Rheumatoid Arthritis: Orbach H

Orbach H, Shoenfeld Y. · No affiliation provided · Harefuah. · Pubmed #12696470 No free full text.

Abstract: Early diagnosis of rheumatoid arthritis (RA) is important since aggressive therapy should begin at an early stage. Diagnosis is made on a clinical basis, supported by the determination of rheumatoid factor (RF). However, RF is also positive in healthy subjects, as well as in other autoimmune and infectious diseases. Two other diagnostic markers with a high specificity for RA, antiperinuclear factor (APF) and antikeratin antibodies (AKA), are not in general use because of technical difficulties. APF and AKA are antifilaggrin antibodies (AFA) that bind to determinants rich in the unusual amino acid citrulline, generated by posttranscriptional modification of arginine residues by the enzyme peptidylarginine deiminase (PAD). Enzymatic determination of recombinant filaggrin fragments produces linear peptides, which are recognized by RA-specific autoantibodies. After substitution of serine by cysteine, a cyclic peptide is formed. The conformational change mimics the original structure of the filaggrin and enhances the affinity of the antibodies. Recently, an anti-cyclic citrullinated peptide (anti-CCP) ELISA was developed. The sensitivity of this test is usually 51%-68%, with a specificity of about 96%-98% (significantly higher than that of RF). Together with RF, anti-CCP increases the ability to diagnose patients with early RA. The test might help to predict which patients will develop persistent disease with evidence of radiologic lesions. Implementation of the highly specific anti-CCP test in conjunction with RF would enable reliable early diagnosis in some cases and allow the initiation of aggressive therapy with disease modifying anti-rheumatic drugs (DMARDs).

Orbach H, Shoenfeld Y. · Department of Medicine B, Wolfson Medical Center, Holon, Israel. · Autoimmun Rev. · Pubmed #17854745 No free full text.

Abstract: The autoimmune diseases are more common in females. The sex hormones have an important role in this gender bias, mainly estrogen and prolactin (PRL) which modulate the immune response. PRL is secreted from the pituitary gland and other organs and cells mainly the lymphocytes. PRL has an immunostimulatory effect and promotes autoimmunity: PRL impairs the negative selection of autoreactive B lymphocytes occurring during B cell maturation into fully functional B cells. PRL has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens and enhances the production of immunoglobulins and autoantibodies. Hyperprolactinemia (HPRL) is observed in multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE) rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT) and multiple sclerosis (MS). There is no consistent correlation between PRL levels and disease activity. Murine models and small studies in SLE patients suggest some role of dopamine agonists in the therapy of those diseases. The genetic factor may have a role in humans as in animal models. The PRL isoform has an important effect on the bioactivity on prolactin receptors (PRL-Rs).

Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, Carvalho JF, Doria A, Shoenfeld Y. · Department of Medicine B, Wolfson Medical Center, Holon, Israel. · Ann N Y Acad Sci. · Pubmed #17785327 No free full text.

Abstract: The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.

Berkun Y, Abou Atta I, Rubinow A, Orbach H, Levartovsky D, Aamar S, Arbel O, Dresner-Pollak R, Friedman G, Ben-Yehuda A. · Department of Pediatrics, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel. · J Rheumatol. · Pubmed #17611986 No free full text.

Abstract: OBJECTIVE: To investigate the distribution of the A2756G polymorphism of the methionine synthase reductase (MTR) gene in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) compared with a healthy control group; and to examine the relationships among the A2756G polymorphism, plasma total homocysteine (tHcy), serum folate and vitamin B12 levels, disease activity, and MTX toxicity in patients with RA. METHODS: A cross-sectional study was performed on 86 MTX-treated RA patients, consisting of a clinical interview and physical examination to determine disease activity and MTX-related adverse reactions. Genotype analysis of the MTR gene was performed. Fasting plasma tHcy, serum folate, and vitamin B12 levels were measured. Allele and genotype distributions were compared to a healthy control group. RESULTS: The frequency of the 2756GG genotype (16.3%) in the RA study group was higher than that expected in the general population (3.6%; p < 0.000001). This genotype was associated with MTX-induced accelerated rheumatoid nodulosis (MIARN). No association of disease activity variables or plasma homocysteine with MTR A2756G polymorphisms was observed. The MTR 2756GG genotype, low plasma vitamin B12 levels, and the presence of rheumatoid nodules predicted MIARN. No association of nodulosis with any other indicator of disease activity or medical treatment was found. CONCLUSION: In our population of MTX-treated RA patients the 2756GG genotype of the MTR gene was more common than expected and was associated with MIARN.

Breuer GS, Orbach H, Elkayam O, Berkun Y, Paran D, Mates M, Nesher G. · Rheumatology Service, Department of Internal Medicine, Shaare Zedek Medical Center, Jerusalem, Israel. · Isr Med Assoc J. · Pubmed #16599054 links to  free full text

Abstract: BACKGROUND: Complementary and alternative medicine has recently attracted attention due to its widespread use. In a recent study in Israel, almost a half of CAM users in the general population used it for joint diseases or back pain. OBJECTIVE: To evaluate the prevalence of CAM use among patients with defined rheumatic diseases, and analyze the demographic features of CAM users, their reasons for using CAM and the use of specific CAM methods. METHODS: We conducted face-to-face structured interviews of 350 patients attending rheumatology clinics, regarding past or present use of CAM, specifying the various CAM types they used, and reasons for using CAM. Demographic data including age, gender, country of birth and origin, and level of education were also collected. RESULTS: Altogether, 148 patients reported using CAM (42%). In general, homeopathy and acupuncture were the most commonly used types (44% and 41% of the patients, respectively). The mean number of CAM methods per patient was 1.9 +/- 1.1. CAM was more commonly used by patients with advanced education (52% vs. 37% of patients with lower education, P= 0.007). Patients with rheumatoid arthritis used CAM significantly less than patients with other rheumatologic conditions (32% vs. 48%, P= 0.008). CONCLUSION: CAM use is influenced by level of education. The choice of the preferred CAM method among patients with rheumatic diseases seemed to follow the popular CAM methods in the general population, and was not specific to rheumatic diseases.

Shovman O, Gilburd B, Zandman-Goddard G, Sherer Y, Orbach H, Gerli R, Shoenfeld Y. · Center for Autoimmune Diseases, Department of Medicine B, Sheba Medical Center, Israel. · Clin Dev Immunol. · Pubmed #16295525 links to  free full text

Abstract: OBJECTIVE: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). METHODS: We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. RESULTS: The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher frequency of elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. CONCLUSION: The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.

Breuer GS, Orbach H, Elkayam O, Berkun Y, Paran D, Mates M, Nesher G. · Rheumatology Service, Department of Internal Medicine, Shaare-Zedek Medical Center and the Hebrew University Medical School, Jerusalem, Israel. · Clin Exp Rheumatol. · Pubmed #16173249 No free full text.

Abstract: OBJECTIVE: The purpose of this cross-sectional survey was to obtain and analyze data on self-perceived efficacy of different types of complementary alternative medicine (CAM) by patients with various rheumatologic conditions. METHODS: Patients followed in rheumatology outpatient clinics were screened for the use of CAM. Patients reporting the use of CAM were asked to participate in face-to-face structured interviews, specifying the various CAM types they used, and grading their subjective impression of efficacy of each CAM type on a scale of 1-10. RESULTS: 350 consecutive patients were screened and 148 reported using CAM. In general, homeopathy and acupuncture were the most commonly used CAM types (44% and 41% of the CAM users, respectively). The mean number of different CAM methods used by a CAM user was 1.9 +/- 1.1. Patients with fibromyalgia used significantly more CAM methods (2.7 +/- 1.4, p = 0.005). On patients' self-perceived efficacy scale of 1-10, the mean score of the whole group was 5.3 +/- 3.2. Acupuncture and homeopathy achieved significantly higher self-perceived efficacy scores in CAM users with spondylo-arthropathies and osteoarthritis, respectively, when compared to some of the other disease groups. Satisfaction was lowest among CAM users with rheumatoid arthritis, vasculitis and connective tissue diseases. CONCLUSION: In general, CAM users were less than moderately satisfied with self-perceived-efficacy of CAM therapies. However efficacy of specific CAM methods differed significantly among patients in different disease groups.

Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, Abou Atta I, Mevorach D, Friedman G, Ben-Yehuda A. · Department of Paediatrics, Bikur Cholim General Hospital, POB 492, Jerusalem 91004, Israel. · Ann Rheum Dis. · Pubmed #15361376 links to  free full text

Abstract: BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.

Orbach H, Gilburd B, Brickman CM, Gerli R, Shoenfeld Y. · Department of Medicine and Rheumatology Unit, Bikur Cholim Hospital, Jerusalem, Israel. · Isr Med Assoc J. · Pubmed #12455175 links to  free full text

This publication has no abstract.