Rheumatoid Arthritis: Zhang H

Freudenberg JA, Bembas K, Greene MI, Zhang H. · Department of Pathology & Laboratory Medicine, University of Pennsylvania, 252 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6082, USA. · Methods. · Pubmed #18573345 No free full text.

Abstract: Many diseases are easier to treat and control when detected at an early stage of disease progression. Often, disease-related antigens or biomarkers are shed from the primary site and present in the blood. Unfortunately, there are very few tests capable of detecting these rare biomarkers in the blood. A blood test would be very useful to diagnose the disease earlier, monitor effectiveness of treatments, predict recurrence, and monitor recurrence. There is certainly a need to develop assays that are ultra-sensitive, non-invasive, and high-throughput. Here we describe several highly sensitive immunological assays we have developed to detect rare serum antigens. Initially we created an assay named immuno-detection amplified by T7 RNA polymerase (IDAT). To enhance the effectiveness and streamline the procedure, this assay was amended to the facile amplification system termed fluorescent amplification catalyzed by T7 polymerase technique (FACTT). These assays have been used to analyze the tumor antigen HER2 and the prion protein PrPSc. They can also be applied to other tumor markers or antigens from a variety of diseases such as cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and hepatitis. These tests are not limited to testing only serum, but may also be applicable to detecting biomarkers in tissue, saliva, urine, cerebrospinal fluid, etc. Clearly, the FACTT-based technology represents an important step in the detection of rare molecules in fluids or tissues for a variety of diseases.

Sun XF, Zhang H. · Department of Oncology, Institute of Biomedicine and Surgery, University of Linköping, Linköping, Sweden. · Histol Histopathol. · Pubmed #17701919 No free full text.

Abstract: Nuclear factor-kappaB (NF-kappaB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-kappaB is inhibited by binding to NF-kappaB inhibitor (IkappaB), and imbalance of NF-kappaB and IkappaB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.

Lu AP, Wu P, Ju DH, Jia HW, Li S, Xu SJ, Zhao N, Xiao C, Wu H, Teng JR, Li Y, Wang SJ, Zhou GQ, Zhang H, Wang AM. · Institute Of Basic Theory, China Acaemy Of Tradtional Chinese Medicine · Zhongguo Zhong Yao Za Zhi. · Pubmed #15988837 No free full text.

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Liang Q, Tang T, Zhang H. · Institute of Combined Traditional Chinese and Western Medicine, Hunan Medical University, Changsha 410008. · Hunan Yi Ke Da Xue Xue Bao. · Pubmed #12212115 No free full text.

Abstract: Ninety-six patients with rheumatoid arthritis(RA) on active phase were divided into BZX-treated group(BZXG) and methotrexate-treated group(MTXG). The results showed that after 1-month treatment, symptoms and signs, such as joint tenderness, arthralgia, arthroncus, of patients in BZXG improved notably(P < 0.01 or P < 0.05), while those of patients in MTXG did not improve, there was significant difference between these two groups(P < 0.01 or P < 0.05). After 3-month treatment, these symptoms and signs improved in both groups(P < 0.01 or P < 0.05), but BZX had a better effect than MTX. ESR, CRP, RF, C3, IgG, IgA and IgM decreased significantly in both groups after treatment(P < 0.01 or P < 0.05), ESR, CRP in BZXG decreased more and faster than those in MTXG. In BZXG the obviously efficient rat was 70%, the total efficacy rate was 94%, while in MTXG was 52% and 87% respectively. It is indicated that BZX can improve symptoms and signs of patients with RA, has better and faster effects on acute phase reaction than MTX; and it has anti-immunologic effects similar to MTX, and has no obvious side effect.

Shi Y, Zhang H, Du X, Zhang M, Yin Y, Zhou C, Song S, Fu X, Li S, Liu Y, Li H, Li X, Wu X, Zhu Y. · Experimental Pharmaceutical Factory, China Academy of Traditional Chinese Medicine, Beijing. · J Tradit Chin Med. · Pubmed #10921143 No free full text.

Abstract: The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120 patients with rheumatoid arthritis were observed in this clinical trial by the randomized double blind method. Both the observed group and the control group each had 60 patients. In the observed group treated with the Tong Luo Kai Bi Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly, 26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi Tablets had much better therapeutic effectiveness clinically than the Rheumatic Semen Strychni Tablets (P < 0.05).

Han W, Zhang H. · Department of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing, 100035, P.R. China. · Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. · Pubmed #19275103 No free full text.

Abstract: OBJECTIVE: To study the operative methods and therapeutic effects of acetabulum reinforcement ring in the reconstruction of acetabular defects in primary and revisional artificial hip replacement. METHODS: From November 2000 to July 2005, 14 cases (15 hips) of severe acetabular defects in artificial hip replacement were treated with acetabulum reinforcement ring combined autogenous or allogenic bone transplantation, including 7 males and 8 females aged 34-72 years with an average of 55 years. Among them, 9 cases (9 hips) underwent artificial hip joint revision, which was 3-22 years (average 8.9 years) far away from their primary replacement, and 5 cases (6 hips) received primary replacement, including 1 case of rheumatoid arthritis of both hips, 1 osteoarthritis caused by acetabular dysplasia, 1 femoral head resection due to debridement of hip infection, 1 nonunion of acetabulum old fracture with the center dislocation of femoral head and 1 old acetabulum fracture. The disease course was 2-25 years (average 11.6 years). According to the American Academy of Orthopaedic Surgeons (AAOS) classification, the acetabulum defects of 7 hips were categorized into Type II, 6 hips were Type III and 2 hips were Type IV. Harris score was (59.1 +/- 15.4) points preoperatively. RESULTS: All wounds were healed by first intention. The symptom of sciatic nerve simulation was occurred in 1 case and was relieved after taking neuroprotective drug for 5 months. All the cases were followed up for 33-90 months (average 51.3 months). Harris score at the final follow-up was (81.9 +/- 10.4) points, indicating there was a significant difference between before and after operation (P < 0.01). X-ray film demonstrated that the displacement of acetabulum reinforcement ring and acetabular cup was less than 5 mm, the rotation was less than 5 degrees, and there was no progressive radiolucent zone around acetabulum and screw. CONCLUSION: Acetabulum reinforcement ring is beneficial to reconstruct severe acetabular defects, improve hip joints' function and provide primary stability for putting acetabular cup into an ideal biomechanical position.

Reiss AB, Carsons SE, Anwar K, Rao S, Edelman SD, Zhang H, Fernandez P, Cronstein BN, Chan ES. · Vascular Biology Institute, Winthrop-University Hospital, Mineola, New York 11501, USA. · Arthritis Rheum. · Pubmed #19035488 No free full text.

Abstract: OBJECTIVE: To determine whether methotrexate (MTX) can overcome the atherogenic effects of cyclooxygenase 2 (COX-2) inhibitors and interferon-gamma (IFNgamma), both of which suppress cholesterol efflux protein and promote foam cell transformation in human THP-1 monocyte/macrophages. METHODS: Message and protein levels of the reverse cholesterol transport proteins cholesterol 27-hydroxylase and ATP-binding cassette transporter A1 (ABCA1) in THP-1 cells were evaluated by real-time polymerase chain reaction and immunoblot, respectively. Expression was evaluated in cells incubated in the presence or absence of the COX-2 inhibitor NS398 or IFNgamma, with and without MTX. Foam cell transformation of lipid-laden THP-1 macrophages was detected with oil red O staining and light microscopy. RESULTS: MTX increased 27-hydroxylase message and completely blocked NS398-induced down-regulation of 27-hydroxylase (mean +/- SEM 112.8 +/- 13.1% for NS398 plus MTX versus 71.1 +/- 4.3% for NS398 alone; P < 0.01). MTX also negated COX-2 inhibitor-mediated down-regulation of ABCA1. The ability of MTX to reverse inhibitory effects on 27-hydroxylase and ABCA1 was blocked by the adenosine A2A receptor-specific antagonist ZM241385. MTX also prevented NS398 and IFNgamma from increasing transformation of lipid-laden THP-1 macrophages into foam cells. CONCLUSION: This study provides evidence supporting the notion of an atheroprotective effect of MTX. Through adenosine A2A receptor activation, MTX promotes reverse cholesterol transport and limits foam cell formation in THP-1 macrophages. This is the first reported evidence that any commonly used medication can increase expression of antiatherogenic reverse cholesterol transport proteins and can counteract the effects of COX-2 inhibition. Our results suggest that one mechanism by which MTX protects against cardiovascular disease in rheumatoid arthritis patients is through facilitation of cholesterol outflow from cells of the artery wall.

Fan LY, Wang WJ, Wang Q, Zong M, Yang L, Zhang H, Sun LS, Lu TB, Han J. · Department of Clinical Laboratory, Shanghai East Hospital, Tong Ji University, Shanghai, China. · Tissue Antigens. · Pubmed #18764812 No free full text.

Abstract: To evaluate the association of single-nucleotide polymorphisms (SNPs) in PADI4 mRNA with rheumatoid arthritis (RA) in a Chinese population, we examined the distribution of four exonic SNPs of the PADI4 gene (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C and padi4_104*T/C) and PADI4 gene expression in 70 RA patients and 81 controls. Increased RA susceptibility was associated with the minor alleles of padi4_89 (P = 0.012), padi4_90 (P = 0.002), padi4_104 (P = 0.001) and the functional haplotype carrying the four minor alleles (P = 0.008). Human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles were also associated with increased RA susceptibility, and the individuals with minor alleles of four exonic SNPs and SE alleles showed more increased RA susceptibility. The PADI4 expression was significantly higher in RA patients than in controls (P < 0.001). HLA-DRB1 SE alleles and the genotypes carrying the minor alleles of four SNPs were associated with increased PADI4 expression. It is concluded that PADI4 SNPs, functional haplotype and PADI4 expression may contribute to an inherited predisposition to RA in a Chinese population.

Matsumoto I, Zhang H, Yasukochi T, Iwanami K, Tanaka Y, Inoue A, Goto D, Ito S, Tsutsumi A, Sumida T. · Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba 305-8575, Japan. · Arthritis Res Ther. · Pubmed #18534002 links to  free full text

Abstract: INTRODUCTION: Immunization with glucose-6-phosphate isomerase (GPI) induces severe arthritis in DBA/1 mice. The present study was designed to identify the cytokines and co-stimulatory molecules involved in the development of GPI-induced arthritis. METHODS: Arthritis was induced in DBA/1 mice with 300 microg human recombinant GPI. CD4+ T cells and antigen-presenting cells from splenocytes of arthritic mice were cultured in the presence of GPI. Tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12 levels were assessed using cytometric bead array. Monoclonal antibodies to TNF-alpha, IFN-gamma, IL-12, CD40L, inducible co-stimulator (ICOS), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (CTLA-4Ig) were used to block TNF-alpha and IFN-gamma production, examine clinical index in mice with GPI-induced arthritis, and determine anti-GPI antibody production. RESULTS: Large amounts of TNF-alpha and IFN-gamma and small amounts of IL-2 and IL-6 were produced by splenocytes from mice with GPI-induced arthritis. Anti-TNF-alpha mAbs and CTLA-4Ig suppressed TNF-alpha production, whereas anti-IFN-gamma mAbs, anti-IL-12 mAbs, and CTLA-4 Ig inhibited IFN-gamma production. A single injection of anti-TNF-alpha and anti-IL-6 mAbs and two injections of CTLA-4Ig reduced the severity of arthritis in mice, whereas injections of anti-IFN-gamma and anti-IL-12 mAbs tended to exacerbate arthritis. Therapeutic efficacy tended to correlate with reduction in anti-GPI antibodies. CONCLUSION: TNF-alpha and IL-6 play an important role in GPI-induced arthritis, whereas IFN-gamma appears to function as a regulator of arthritis. Because the therapeutic effects of the tested molecules used in this study are similar to those in patients with rheumatoid arthritis, GPI-induced arthritis appears to be a suitable tool with which to examine the effect of various therapies on rheumatoid arthritis.

Yu DF, Chen Y, Han JM, Zhang H, Chen XP, Zou WJ, Liang LY, Xu CC, Liu ZG. · State Key Laboratory of Ophthalmology of Sun Yat-Sen University, Zhongshan Ophthalmic Center, Ocular Surface Center of Sun Yat-Sen University, Guangzhou, China. · Exp Eye Res. · Pubmed #18184611 No free full text.

Abstract: This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease.

Li X, Li X, Qian L, Wang G, Zhang H, Wang X, Chen K, Zhai Z, Li Q, Wang Y, Harris DC. · Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, Hefei, Anhui Province, China. · J Rheumatol. · Pubmed #18050367 No free full text.

Abstract: OBJECTIVE: To investigate the abnormalities of T regulatory cells (Treg) in salivary glands and peripheral blood in patients with primary Sjögren's syndrome (pSS). METHODS: Levels of CD4+CD25+ high T cells of the peripheral blood of 52 patients with pSS were measured by flow-cytometric assay. Lower lip salivary gland biopsies were examined by immunohistochemistry, using monoclonal mouse anti-human antibodies [CD25, CD4, CD8, CD68, forkhead transcription factor (Foxp3)] in 30 patients with pSS. Using real-time polymerase chain reaction, Foxp3 messenger RNA expression was assessed in the salivary glands and CD4+ T cells from peripheral blood. RESULTS: Many inflammatory cells, predominantly CD4+ and CD8+ T cells and macrophages, were found in salivary glands of patients with SS, but CD4+CD25+ Treg numbers and Foxp3 expression were markedly reduced in those biopsy samples. Levels of CD4+CD25+ high T cells and Foxp3 expression in peripheral blood of patients with pSS were significantly lower than in healthy controls. However, the inhibitory function of CD4+CD25+ T cells in pSS was unchanged compared to that of controls. Peripheral CD4+CD25+ high T cell numbers in pSS did not correlate with Schirmer's test and salivary flow rate, or with the presence or absence of anti-SSA/SSB antibodies and immunoglobulin level. CONCLUSION: The remarkable reduction of Treg numbers in salivary glands and reduction of CD4+CD25+ high T cells in peripheral blood suggests a possible role for absence of Treg in the pathogenesis of salivary gland destruction in pSS.

Li XM, Li XP, Qian L, Wang GS, Zhang H, Wang XQ, Chen K, Wang YP. · Department of Rheumatology and Immunology, University Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #17959073 No free full text.

Abstract: OBJECTIVE: To investigate the expression of forkhead box protein P3 (Foxp3) in the peripheral blood and salivary gland of patients with Sjogren's Syndrome (SS). METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine Foxp3mRNA expression in the CD(4)(+) T cells and the salivary glands from 6 primary SS patients and 6 normal controls. Serial sections of biopsied salivary gland (SG) were examined with immunohistochemistry, using monoclonal mouse anti-human CD(4) and Foxp3 in 6 healthy controls and 31 primary SS patients. RESULTS: Significant difference in the number of infiltrating CD(4)(+) T cells was noted in the salivary glands of the patients and controls, but Foxp3(+)CD(4)(+) T cells were almost absent in those biopsy samples. Foxp3mRNA expression in the blood of SS patients was significantly lower than that in normal controls (0.21 +/- 0.17 vs 1.32 +/- 0.38, P < 0.0184). Foxp3mRNA expression was not detectable in the tissue of the salivary glands (n = 6). CONCLUSION: The absence of Foxp3(+)CD(4)(+) T cells in salivary glands with reduction of Foxp3mRNA expression in peripheral blood suggests an important role of Foxp3 in the pathogenesis of SS.

Li XM, Li XP, Qian L, Wang GS, Zhang H, Zhei ZM, Li Q, Chen K, Wang XQ, Wang YP. · Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, Hefei 230001, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #17672966 No free full text.

Abstract: OBJECTIVE: To investigate the expression of CD(4)(+) CD(25)(+) regulatory T cells (Tregs) in the peripheral blood and salivary gland of patients with primary Sjögren's syndrome (pSS). METHODS: Samples of peripheral venous blood were collected from 57 newly diagnosed pSS patients, 1 male and 56 females, aged 47 (20 approximately 76), and 46 healthy controls. The levels of CD(4)(+) CD(25)(+) T regulatory cells and CD(4)(+) CD(25)(high) T regulatory cells in the peripheral blood were measured by flow-cytometric assay. Biopsy specimens of labial gland were collected from the 57 patients and 6 healthy person or patients with labial gland cyst. Pathological examination was conducted by light microscopy. Immunohistochemistry was conducted, by using monoclonal mouse anti-human to detect the expression of CD25, CD4, CD8, and CD68. Western blotting was used to detect the levels of IgG, IgM, and IgA. The salivary flow rate was measured. Schirmer's test was used to measure the tear flow rate. RESULTS: The level of CD(4)(+) CD(25)(+) Tregs in the blood of pSS patients was 6.9% (2.84% - 13.50%), significantly lower than that of the healthy controls [10.9% (5.77% - 15.3%), P < 0.001). The level of CD(4)(+) CD(25)(high) Tregs the blood of pSS patients was 0.6% (0.001% - 1.83%), significantly lower than that of the healthy controls [1.1% (0.13% - 2.45%), P < 0.001]. Immunohistochemistry showed that most of the infiltrating lymphocytes in the labial gland of the pSS patients were CD(4)(+) T cells, and there was no CD(25)(+) T cell in both groups. The numbers of peripheral CD(4)(+) CD(25)(+) T cells and CD(4)(+) CD(25)(high) Tregs in the pSS patients were not correlated with the tear flow rate, salivary flow rate, anti-SS-A/SS-B antibodies, and immunoglobulin level. CONCLUSION: The pSS patients show an absence of CD(4)(+) CD(25)(+) T cell in the labial gland of pSS patients, and reduction of the numbers of CD(4)(+) CD(25)(+) and CD(4)(+) CD(25)(high) Tregs in the peripheral blood, which suggests that Tregs play an important role in the pathogenesis of salivary gland destruction in SS.

Chen Q, Li X, He W, Zhang H, Gao A, Cheng Y, Lei J, Li S, Zeng L. · Laboratory of Molecular Diagnostics, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China. · Clin Exp Immunol. · Pubmed #17614976 links to  free full text

Abstract: Alpha-fodrin, an intracellular organ-specific cytoskeleton protein, was identified recently as an autoantigen associated with Sicca- and Sjögren's syndrome (SS). Identification of the antigenic determinants of alpha-fodrin is a prerequisite to developing highly sensitive and specific anti-alpha-fodrin antibodies, which provides potential means for the diagnosis of primary Sjögren's syndrome (pSS) in patients. Based on the structure and predicted antigenic sites of alpha-fodrin protein with 560 amino acids (alpha-fodrin 560), we prepared a set of overlapping recombinant protein fragments covering antigenic epitopes and synthesized a set of peptides derived from the alpha-fodrin protein. These recombinant proteins and synthesized peptides were subjected to screening with pSS patients sera, respectively. The peptide with the strongest immunoreactivity was used as antigenic peptide to define further the role of anti-alpha-fodrin-peptide antibodies in the sera of 135 patients with pSS, 48 patients with systemic lupus erythematosus (SLE), 88 patients with rheumatoid arthritis (RA) and 83 normal controls. Our data showed that the N-terminal peptide of amino acids 46-59 (N46) of alpha-fodrin 560 was the epitope with strongest antigenicity. The prevalences of anti-N46 peptide antibodies (alpha-N46PA) in patients with pSS, SLE, RA and normal controls were 78.5%, 10.4%, 21.6% and 6.0%, respectively. The sensitivity and specificity of the autoantibodies in pSS were 78.5% and 86.8%, respectively. These results suggest the alpha-N46PA which shows highest sensitivity and specificity is of significance to develop an effective diagnostic approach for pSS.

Zhang H, Gao G, Clayburne G, Schumacher HR. · Division of Pharmaceutics and Industry Pharmacy, School of Pharmacy, Long Island University, Brooklyn, NY, USA. · Arthritis Res Ther. · Pubmed #16277676 links to  free full text

Abstract: Surgical synovectomy to remove the inflammatory synovium can temporarily ameliorate rheumatoid inflammation and delay the progress of joint destruction. An efficient medically induced programmed cell death (apoptosis) in the rheumatoid synovium might play a role similar to synovectomy but without surgical tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of apoptotic cells in mouse and rabbit arthritic synovium. In this study, we investigated whether repeated FasL gene transfer could remove human inflammatory synovial tissue in situ and function as a molecular synovectomy. Briefly, specimens of human synovium from joint replacement surgeries and synovectomies of rheumatoid arthritis (RA) patients were grafted subcutaneously into male C.B-17 severe combined immunodeficiency (SCID) mice. Injections of a recombinant FasL adenovirus (Ad-FasL) into the grafted synovial tissue at the dosage of 10(11) particles per mouse were performed every two weeks. Three days after the fifth virus injection, the mice were euthanized by CO2 inhalation and the human synovial tissues were collected, weighed and further examined. Compared to the control adenovirus-LacZ (Ad-LacZ) and phosphate buffered saline (PBS) injected RA synovium, the Ad-FasL injected RA synovium was dramatically reduced in size and weight (P < 0.005). The number of both synoviocytes & mononuclear cells was significantly reduced. Interestingly, an approximate 15-fold increased frequency of apoptotic cells was observed in RA synovium three days after Ad-FasL injection, compared with control tissues. In summary, our in vivo investigation of gene transfer to human synovium in SCID mice suggests that repeated intra-articular gene transfer of an apoptosis inducer, such as FasL, may function as a 'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an early stage of RA.

Matsumoto I, Zhang H, Muraki Y, Hayashi T, Yasukochi T, Kori Y, Goto D, Ito S, Tsutsumi A, Sumida T. · Clinical Immunology, University of Tsukuba, Ibaraki, Japan. · Arthritis Res Ther. · Pubmed #16277670 links to  free full text

Abstract: Anti-glucose-6-phosphate isomerase (GPI) antibodies are known to be arthritogenic autoantibodies in K/BxN mice, although some groups have reported that few healthy humans retain these antibodies. The expression of Fcgamma receptors (FcgammaRs) is genetically regulated and has strong implications for the development of experimental arthritis. The interaction between immune complexes and FcgammaRs might therefore be involved in the pathogenesis of some arthritic conditions. To explore the relationship between functional polymorphisms in FcgammaRs (FCGR3A-158V/F and FCGR2A-131H/R) and arthritis in individuals positive for anti-GPI antibodies, we evaluated these individuals with respect to FCGR genotype. Genotyping for FCGR3A-158V/F and FCGR2A-131H/R was performed by PCR amplification of the polymorphic site, followed by site specific restriction digestion using the genome of 187 Japanese patients with rheumatoid arthritis (including 23 who were anti-GPI antibody positive) and 158 Japanese healthy individuals (including nine who were anti-GPI antibody positive). We report here on the association of FCGR3A-158V/F functional polymorphism with anti-GPI antibody positive status. Eight out of nine healthy individuals who were positive for anti-GPI antibodies possessed the homozygous, low affinity genotype FCGR3A-158F (odds ratio = 0.09, 95% confidence interval 0.01-0.89; P = 0.0199), and probably were 'protected' from arthritogenic antibodies. Moreover, among those who were homozygous for the high affinity genotype FCGR3A-158V/V, there were clear differences in anti-human and anti-rabbit GPI titres between patients with rheumatoid arthritis and healthy subjects (P = 0.0027 and P = 0.0015, respectively). Our findings provide a molecular model of the genetic regulation of autoantibody-induced arthritis by allele-specific affinity of the FcgammaRs.

Li W, Yin J, Zhou Y, Dou B, Zhang H, Zhou Y. · Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Beijing 100035, China. · Zhonghua Wai Ke Za Zhi. · Pubmed #16201170 No free full text.

Abstract: OBJECTIVE: To evaluate the middle-term results of posterior stabilized knee arthroplasty (PSKA). METHODS: From July 1995 to July 2000, 19 knees of 18 patients were replaced with posterior stabilized prosthesis (Insall-Burstein II). Among the patients, 2 were male, and 16 female. Their average age was 62.5 years (44-78 years). One patient was operated on bilaterally. Preoperative diagnosis revealed osteoarthritis in 16 knees, and rheumatoid arthritis in 3 knees. Four knees demonstrated severe bone deficiency during surgery. Before operation, 15 of the rest knees were varusly deformed, 4 were valgusly deformed, and 8 had flexion contracture. Two patients underwent surgery previously. 17 patients (18 knees) were followed-up for 41-60 months, each of them was evaluated with the Special Surgery Knee Scoring System. RESULTS: Average preoperative scores increased from 62 preoperatively to 89 postoperatively. The range of motion was significantly improved from 91 degrees preoperatively to 115 degrees postoperatively. Eleven knees were rated as excellent, 5 good, 1 fair, and 1 poor. The excellent and good rate was 88.9%. CONCLUSIONS: With its design features, PSKA can effectively improve the range of motion and maximum flexion angle without compromising posterior stability. PSKA is suitable for both primary and revision total knee arthroplasty but caution should be taken for patellar complications.

Suzuki T, Muraki Y, Yasukochi T, Zhang H, Kori Y, Wakamatsu E, Hayashi T, Goto D, Ito S, Tsutsumi A, Sumichika H, Sumida T, Matsumoto I. · Clinical Immunology, Major of Advanced Biomedical Applications, Graduate of Comprehensive Human Sciences, University of Tsukuba, University of Tsukuba, 1-1-1 Tenodai, Ibaraki 305-8575, Japan. · Autoimmun Rev. · Pubmed #16137614 No free full text.

Abstract: Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.

Ichikawa K, Liu W, Fleck M, Zhang H, Zhao L, Ohtsuka T, Wang Z, Liu D, Mountz JD, Ohtsuki M, Koopman WJ, Kimberly R, Zhou T. · Biomedical Research Laboratories, Sankyo Company, Limited, Tokyo, Japan. · J Immunol. · Pubmed #12847280 links to  free full text

Abstract: TRAIL has been proposed as an anti-inflammatory cytokine in animal models of rheumatoid arthritis (RA). Using two agonistic mAbs specific for TRAIL-R1 (DR4) and TRAIL-R2 (DR5), we examined the expression and function of these death receptors in RA synovial fibroblast cells. The synovial tissues and primary synovial fibroblast cells isolated from patients with RA, but not those isolated from patients with osteoarthritis, selectively expressed high levels of cell surface DR5 and were highly susceptible to anti-DR5 Ab (TRA-8)-mediated apoptosis. In contrast, RA synoviocytes did not show increased expression of TRAIL-R1 (DR4), nor was there any difference in expression of Fas between RA and osteoarthritis synovial cells. In vitro TRA-8 induced apoptosis of RA synovial cells and inhibited production of matrix metalloproteinases induced by pro-inflammatory cytokines. In vivo TRA-8 effectively inhibited hypercellularity of a SV40-transformed RA synovial cell line and completely prevented bone erosion and cartilage destruction induced by these cells. These results indicate that increased DR5 expression and susceptibility to DR5-mediated apoptosis are characteristic of the proliferating synovial cells in RA. As highly proliferative transformed-appearing RA synovial cells play a crucial role in bone erosion and cartilage destruction in RA, the specific targeting of DR5 on RA synovial cells with an agonistic anti-DR5 Ab may be a potential therapy for RA.

Gérard HC, Wang Z, Wang GF, El-Gabalawy H, Goldbach-Mansky R, Li Y, Majeed W, Zhang H, Ngai N, Hudson AP, Schumacher HR. · Wayne State University School of Medicine, Detroit, Michigan 48201, USA. · Arthritis Rheum. · Pubmed #11465721 links to  free full text

Abstract: OBJECTIVE: We and others have reported the presence of Chlamydia and other bacterial species in joint specimens from patients with reactive arthritis (ReA). The present study was conducted to investigate whether bacteria other than those specified by diagnostic criteria for ReA could be identified in synovial fluid (SF) or tissue from patients with various arthritides, and whether the presence of such organisms corresponds to particular clinical characteristics in any patient set or subset. METHODS: DNA in synovial biopsy samples and SF obtained from 237 patients with various arthritides, including ReA, rheumatoid arthritis, and undifferentiated oligoarthritis, was assayed by polymerase chain reaction (PCR) using "panbacterial" primers; we chose only samples known to be PCR negative for Chlamydia, Borrelia, and Mycoplasma species. PCR products were cloned, and cloned amplicons from each sample were sequenced; DNA sequences were compared against all others in GenBank for identification of bacterial species involved. RESULTS: Ten percent of patient samples were PCR positive in panbacterial screening assays. Bacterial species identified belonged to the genera Neisseria, Acinetobacter, Moraxella, Salmonella, Pseudomonas, and others. Thirty-five percent of PCR-positive patients showed the presence of DNA from more than a single bacterial species in synovium; overall, however, we could identify no clear relationship between specific single or multiple bacterial species in the synovium and any general clinical characteristics of any individual or group of patients. CONCLUSION: This analysis provides the first systematic attempt to relate bacterial nucleic acids in the synovium to clinical characteristics, joint findings, and outcomes. Many patients with arthritis have bacterial DNA in the joint, and, in some cases, DNA from more than a single species is present. However, except for 1 case of a control patient with staphylococcal septic arthritis, it is not clear from the present study whether the synovial presence of such organisms is related to disease pathogenesis or evolution in any or all cases.

Kori Y, Matsumoto I, Zhang H, Yasukochi T, Hayashi T, Iwanami K, Goto D, Ito S, Tsutsumi A, Sumida T. · No affiliation provided · Ann Rheum Dis. · Pubmed #16769785 links to  free full text

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