Hepatitis: Shoenfeld Y

Amital H, Eric Gershwin M, Shoenfeld Y. · No affiliation provided · Semin Arthritis Rheum. · Pubmed #16765709 No free full text.

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Berkun Y, Gershwin ME, Shoenfeld Y. · No affiliation provided · Isr Med Assoc J. · Pubmed #15847210 links to  free full text

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Selmi C, Battezzati PM, Gershwin ME, Tishler M, Shoenfeld Y. · No affiliation provided · Autoimmun Rev. · Pubmed #15722253 No free full text.

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Belizna CC, Hamidou MA, Levesque H, Guillevin L, Shoenfeld Y. · Internal Medicine Department, CHU Rouen, Rouen, France. · Rheumatology (Oxford). · Pubmed #19258377 No free full text.

Abstract: Vasculitis may be associated with infection, immunization or anti-microbial drugs. Infections are responsible for a number of different types of vasculitis. Conversely, patients with vasculitis may develop infections, which sometimes mimic relapse. The aim of this review is to summarize the various aspects of the inter-relationship between vasculitis and infection, and the physiopathological mechanisms involved, in light of our current knowledge from animal models. Currently, a causal relationship between infection and vasculitis has only been established in a few instances and many mechanisms remain hypothetical. This inter-relationship is further assessed from the point of view of clinical presentation and therapeutic options, based on case reports and prospective observational data.

de Carvalho JF, Pereira RM, Shoenfeld Y. · Rheumatology Division, São Paulo University School of Medicine, São Paulo, Brazil. · Eur J Intern Med. · Pubmed #19046721 No free full text.

Abstract: The authors report a patient who developed systemic polyarteritis nodosa two months after hepatitis B vaccination and review the literature concerning this vaccination and the development of autoimmune conditions, mainly vasculitis. A 14-year-old boy who had no relevant previous history and who was not taking any drugs presented with a livedo reticularis, fever, loss of weight, testicular pain, and paresthesias two months after receiving the third dose of a hepatitis B vaccination. Inflammatory parameters (ESR and CRP) were high. The patient met the ACR diagnostic criteria for polyarteritis nodosa. He received corticosteroids and immunosuppressants and showed improvement. After reviewing the 27 cases of vasculitis after hepatitis B vaccination reported in the current literature, the authors suggest that, in some cases, vaccination may be the triggering factor for vasculitis in individuals with a genetic predisposition. Physicians should be aware of this possible association.

de Carvalho JF, Shoenfeld Y. · Rheumatology Division, São Paulo University School of Medicine, São Paulo, Brazil. · Eur J Intern Med. · Pubmed #18549949 No free full text.

Abstract: The case reported refers to a patient who developed status epilepticus in the day of her third dose of hepatitis B vaccination and we review the literature on this subject. A 12 year-old girl, without a relevant previous history, taking no drugs, developed a seizure attack followed by unconsciousness, and eventually died after three days of her third dose of hepatitis B (HB) vaccination. Autopsy study revealed cerebral edema with congestion and herniation and diffuse interstitial type pneumonitis. There seem to be a straight forward time relationship between the third HB vaccine, the event of convulsion and the sudden death of the patient. We suggest that, in some cases, vaccination may be the triggering factor for autoimmune and neurological disturbances in genetically predisposed individuals and physicians should be aware of this possible association.

Ram M, Shoenfeld Y. · Center for Autoimmune Diseases and Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel. · Isr Med Assoc J. · Pubmed #18300577 links to  free full text

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Barzilai O, Ram M, Shoenfeld Y. · Center for Autoimmune Diseases, Department of Medicine B, Sheba Medical Center, Israel. · Curr Opin Rheumatol. · Pubmed #17917546 No free full text.

Abstract: PURPOSE OF REVIEW: To review the current literature and summarize the main principles found between viral infections and the subsequent production of autoantibodies. RECENT FINDINGS: We concentrate on recent findings involving three viral agents, one of which is Epstein-Barr virus, which has been associated with many autoimmune diseases and is classically considered to induce systemic lupus erythematosus. As we will discuss, this occurs through molecular mimicry between Epstein-Barr virus nuclear antigen 1 and lupus-specific antigens such as Ro, La or dsDNA, through induction of Toll-like receptor hypersensitivity by Epstein-Barr virus latent membrane protein 2A or by creating immortal B and T cells by loss of apoptosis. Hepatitis B virus was found to share amino acid sequences with different autoantigens. Tissue damage and the release of intracellular components is just another example of the autoantibody production caused by this virus. Cytomegalovirus has often been controversially associated with several autoimmune diseases and, although is the least understood viral infection of the three, appears to be somewhat suspicious. SUMMARY: Understanding the infectious origin of autoimmune diseases is important as we aim to identify high-risk patients and disrupt this process with vaccines or other medications, ultimately delaying or even preventing the evolution of autoimmune diseases.

Shoenfeld Y. · Department of Medicine B, Center for Autoimmune Diseases, Chaim Sheba Medical Center, 52621 Tel-Hashomer, Israel. · J Autoimmun. · Pubmed #17382516 No free full text.

Abstract: Central Nervous System involvement in Systemic Lupus Erythematosus (CNS-SLE) is very common and ranges between 25%-70% of the patients. The CNS involvement is listed in the ARA criteria for SLE diagnosis. CNS-SLE is associated with more than 20 different autoantibodies. Yet, remarkable among them are the anti-P-ribosomal antibodies (anti-PR). These autoantibodies directed mainly against the carboxy 22 amino acids of the PO, P1 P2 ribosomal phosphoproteins. They are capable of penetrating lived cells and inducing apoptotic changes as well as leading to inhibition of specific cytokine secretion. The titer of the autoantibodies correlate with disease activity, kidney involvement and hepatitis. In this review, the mechanisms involved in CNS involvement and its relationship with anti-P ribosomal antibodies will be described.

Zandman-Goddard G, Shoenfeld Y. · Center for Autoimmune Diseases and Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel. · Autoimmunity. · Pubmed #16373252 No free full text.

Abstract: Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE.

Khamaisi M, Shoenfeld Y, Orbach H. · Department of Internal Medicine B and the Diabetes Center, Hadassah University Hospital, Jerusalem, Israel. · Clin Exp Rheumatol. · Pubmed #15638054 No free full text.

Abstract: A 52-year-old woman developed Guillain-Barré syndrome 10 weeks after immunization with recombinant hepatitis B vaccine. Common infectious causes of GBS were ruled out. The temporal relationship between GBS and hepatitis B virus (HBV) vaccination was suggestive of a vaccine-induced cause. The possible mechanisms of this very, rare complication are discussed.

Zandman-Goddard G, Shoenfeld Y. · Center for Autoimmune Diseases and Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel 52621. · Clin Rev Allergy Immunol. · Pubmed #12794259 No free full text.

Abstract: Infections are common in systemic lupus erythematosus (SLE), and remain a source of mortality. The types of infections (such as pneumonia, urinary tract infection, cellulitis, and sepsis) in SLE patients are similar to the general population and include the same pathogens (Gram-positive and Gram-negative). SLE patients may also develop opportunistic infections, especially when treated with immunosuppressive agents. As a high-risk population, identification and treatment of chronic infections such as tuberculosis, hepatitis B, or human immunodeficiency virus (HIV), are important prior to the institution of immunosuppression to prevent reactivation or exacerbation of the infection. A common caveat is to distinguish between a lupus flare and an acute infection; judicious use of corticosteroids and cytotoxic drugs is critical in limiting infectious complications. The risk factors associated with susceptibility to disease include severe flares, active renal disease, treatment with moderate or high doses of corticosteroids and/or immunosuppressive agents, and others. Genetic factors (complement deficiencies, mannose-binding lectin, Fcgamma III, granulocyte macrophage colony-stimulating factor [GM-CSF], osteopontin) may predispose certain SLE patients to develop infections. Parameters including C-reactive protein (CRP) and adhesion molecules may help to differentiate an infectious disease from an exacerbation of the disease. Finally, the mechanism of molecular mimicry by specific microbial agents may play a role in the induction of SLE.

Borchers AT, Keen CL, Shoenfeld Y, Silva J, Gershwin ME. · Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA. · J Investig Allergol Clin Immunol. · Pubmed #12530114 No free full text.

Abstract: Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease.

Aron-Maor A, Shoenfeld Y. · Department of Internal Medicine B and Center for Autoimmune Diseases, Sheba Medical Center, Sacklea Faculty of Medicine, Tel Aviv University, Tel-Hashomer, Israel. · Lupus. · Pubmed #11315360 No free full text.

Abstract: Vaccination has been perhaps the most important achievement in medicine of the last century. A hoard of infectious diseases that used to claim the lives of many, especially children, have been prevented and some even eradicated. However, it is possible that within this gift there is hidden a 'Trojan Horse'. During the last decade increasing numbers of reports regarding possible autoimmune side effects of vaccination, have been published. The existing data does not link the vaccines and the autoimmune phenomena observed in a causal relationship, nevertheless a temporal connection has been described. In this article we wish to address in particular the possible link between vaccines and systemic lupus erythematosus (SLE), namely two aspects of this inter-relationship: the occurrence of SLE following vaccination and outcome of immunization of known SLE patients.

Shoenfeld Y, Aron-Maor A. · Department of Internal Medicine B, Sheba Medical Center, Tel Hashomer, Israel. · J Autoimmun. · Pubmed #10648110 No free full text.

Abstract: The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine.So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed.Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome).The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this issue (although the temporal relationship (i.e. always 2-3 months following immunization) is impressive).

Siekmann JH, Allen LH, Watnik MR, Nestel P, Neumann CG, Shoenfeld Y, Peter JB, Patnik M, Ansari AA, Coppel RL, Gershwin ME. · Department of Nutrition, University of California, Davis 95616, USA. · Am J Clin Nutr. · Pubmed #12499348 links to  free full text

Abstract: BACKGROUND: Undernutrition is widely perceived to affect the development of an effective immune system. OBJECTIVE: We used a mini-analysis system to quantitate antibody titers and evaluate the sera of 200 Kenyan schoolchildren for antibodies to Helicobacter pylori [isotypes of immunoglobulins A (IgA), G (IgG), and M (IgM)], hepatitis A virus, rotavirus, tetanus toxoid (IgG), and a panel of recombinant malarial antigens (MSP1(19), MSP2, Ag512, MSP4, and MSP5). DESIGN: Children participated in a school-based feeding intervention with meat, milk, or nonanimal-source foods or in a nonintervention control group. Microvolumes (200 mL) of sera were analyzed at baseline and after 1 y. RESULTS: Nearly all children had elevated titers of antibody to H. pylori, hepatitis A virus, rotavirus, and malaria at the outset, despite a high prevalence of apparent biochemical micronutrient deficiencies and stunting, but many had titers of tetanus toxoid IgG antibodies below the protective concentration. Children with low hemoglobin had a greater proportion of elevated H. pylori IgM antibody titers at baseline, which suggests that current infection with H. pylori may be associated with anemia. Compared with the control subjects, only the group eating meat had a significant increase in H. pylori IgM antibodies during the intervention (P = 0.019). No other group comparisons with the control subjects were statistically significant. The additional finding that the sera of some children showed inadequate tetanus-protective antibodies, despite immunization, suggests that the vaccination program was suboptimal. CONCLUSIONS: A large battery of immune assays can be performed on microvolumes of sera. Furthermore, despite evidence of malnutrition, children do develop significant antibody-mediated responses to common pathogens.

Agmon-Levin N, Ram M, Barzilai O, Porat-Katz BS, Parikman R, Selmi C, Gershwin ME, Anaya JM, Youinou P, Bizzaro N, Tincani A, Tzioufas AG, Cervera R, Stojanovich L, Martin J, Gonzalez-Gay MA, Valentini G, Blank M, SanMarco M, Rozman B, Bombardieri S, De Vita S, Shoenfeld Y. · Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. · J Autoimmun. · Pubmed #19356903 No free full text.

Abstract: OBJECTIVE: To evaluate the prevalence of serum antibodies against hepatitis C virus and other infectious agents in a large cohort of well-characterized patients with autoimmune diseases (AID). METHODS: We utilized 1322 sera from patients with 18 different AID and 236 sera from healthy controls from the same countries and with similar age and sex distribution. All sera were tested for the presence of serum anti-hepatitis C virus (HCV) antibodies as well as antibodies directed at other infectious agents and autoantibodies. RESULTS: Anti-HCV antibody was detected in 115/1322 (8.7%) of patients with AID and 0.4% of matched healthy controls (P < 0.0001). The prevalence of anti-HCV antibody was significantly higher in 7/18 different AID (i.e. cryoglobulinemia, mixed cryoglobulinemia pemphigus vulgaris, vasculitis, secondary anti-phospholipid syndrome, Hashimoto's thyroiditis, and inflammatory bowel disease) compared to controls. Patients with AID and serum anti-HCV positivity had an increased prevalence of antibodies against hepatitis B virus, Toxoplasma gondii and Cytomegalovirus as opposed to a lower frequency of serum autoantibodies. CONCLUSIONS: The enhanced prevalence of anti-HCV serum antibodies in AID may suggest a role for HCV in tolerance to breakdown, similarly to its established role in mixed cryoglobulinemia. This immune mediated effect does not rule out the role of other infectious agents.

Nancy AL, Shoenfeld Y. · Center for Autoimmune Diseases, Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel. · Autoimmun Rev. · Pubmed #18725327 No free full text.

Abstract: BACKGROUND: Chronic fatigue syndrome (CFS) that defines by prolonged fatigue and other manifestations, was recently integrated into a spectrum of central sensitivity syndromes including several diseases as fibromylagia. CFS etiology is multi-factorial commonly triggered by infectious agents. Vaccines, induce an immune response similarly to infections, and may trigger just like infections autoimmune diseases, CFS and fibromyalgia. Furthermore vaccines contain an adjuvant which enhances their immune stimulation. CASE PRESENTATION: A 56-year-old woman was diagnosed with CFS accompanied by fibromyalgia, demyelination and autoantibodies. Her illness begun following the 2nd dose of hepatitis-B vaccine, and was aggravated by the 3rd vaccination. She underwent silicone breast implantation 6 years before vaccination with no adverse events. However, between the 2nd and 3rd vaccination she suffered a breast injury with local inflammation. Upon explanation of her breast implants silicone leak was observed. DISCUSSION: Vaccines have been reported to precede CFS mainly following exposure to multiple vaccinations (e.g. the Gulf war syndrome), or as an adverse response to the vaccine adjuvant (e.g. the macrophagic myofasciitis syndrome). Silicone is considered an adjuvant to the immune system, and may induce "the adjuvant disease". Silicone implant, especially silicone leak relationship with autoimmunity and CFS has been the focus of considerable debates. CONCLUSION: Our patient illness started following hepatitis-B vaccine, suggesting that it was caused or accelerated by vaccination. In parallel to vaccination our patient suffered from breast injury, which might represent the time of silicone leak. The exposure to the adjuvant, silicone, might have augmented her immune response to the vaccine. To the best of our knowledge this is the first case of combined adverse effect to vaccine and silicone. Vaccine safety in individuals with silicone implants requires further studies.

Ram M, Anaya JM, Barzilai O, Izhaky D, Porat Katz BS, Blank M, Shoenfeld Y. · Center for Autoimmune Diseases, Department of Medicine 'B', Sheba Medical Center, Israel. · Autoimmun Rev. · Pubmed #18603025 No free full text.

Abstract: BACKGROUND: The etiology of autoimmune diseases is not fully clarified and the mechanisms underlying their initiation and progression are still obscure. It is becoming clear that in a genetic susceptible individual an environmental trigger such as infectious agent in general and viruses in particular could initiate the development of an autoimmune disease. Hepatitis B virus (HBV) is notorious in its association with diverse autoimmune diseases. Therefore, we aimed to determine the presence of hepatitis B core antibody (HBcAb), a seromarker for past or present infection with HBV, in a large number of sera collected from patients with different autoimmune diseases. METHODS: A cohort of 675 sera samples of 5 different autoimmune diseases and healthy donors were screened for evidence of a prior infection with HBV. All samples were tested for hepatitis B core antibody (IgG) using the Monolisa anti-HBc PLUS commercial kit (Bio-Rad, Hercules, San Francisco, USA). RESULTS: Lower percentage of HBcAb was found in sera of the autoimmune diseases when compared to normal controls. Fifteen (10.7%) from 140 normal controls were found positive for the presence of HBcAb. Two (2%) out of 98 multiple sclerosis (MS) sera were positive for the presence of HBcAb (OR: 0.17, 95%CI: 0.03-0.77, p=0.01), 3 (2.5%) out of 117 systemic lupus erythematosus (SLE) sera (OR: 0.2, 95%CI: 0.06-0.77, p=0.01), 4 (4.5%) out of 89 type 1 diabetes (T1D), 5 (6.1%) from 82 Sjogren's syndrome (SS) sera and 12 (8%) from 149 rheumatoid arthritis (RA) sera were positive for the presence of HBcAb. CONCLUSIONS: Our data divulge an unexpected low percentage of antibodies to HBcAg in patients with SLE, MS and T1D in comparison to healthy matched donors. This finding may raise a protective role to HBV in some autoimmune diseases i.e. hygiene theory.

Zandman-Goddard G, Berkun Y, Barzilai O, Boaz M, Ram M, Anaya JM, Shoenfeld Y. · Department of Medicine C, Wolfson Medical Center, Holon, Israel. · Lupus. · Pubmed #18490412 No free full text.

Abstract: Infections can act as environmental triggers inducing or promoting systemic lupus erythematosus (SLE) in genetically predisposed individuals. The aim of the present study was to compare the titres of antibodies (Abs) to infectious agents with neuropsychiatric (NPSLE) clinical manifestations. The sera of 260 individuals (120 patients with SLE and 140 geographic controls) were evaluated for the titres of Epstein bar virus (EBV), cytomegalovirus (CMV), toxoplasma, rubella and syphilis Abs using the BioPlex 2200 Multiplexed Immunoassay method (BioRad) and by the ELISA method for Helicobacter pylori and Hepatitis B core Ag. All BioPlex 2200 kits used were in developmental stages. Data analysis was performed using SPSS 9.0 statistical analysis software (SPSS Inc., Chicago, IL, USA, 1999). Correlation analysis indicated that rubella IgM Ab titres were marginally, positively associated with psychosis (P = 0.09). No other associations were detected between the 17 infectious Abs and five NP manifestations. When the positivity cut-off for anti-rubella IgM Abs was set at three standard deviations above normal, three positive subjects were identified: one patient with psychosis and one with depression, for a total NPSLE prevalence of 33.3%. On the contrary, the prevalence of NPSLE in the remaining subjects was 6.5%. Marginally significant correlations between elevated titres of rubella IgM Ab with psychosis and depression were found. Although this nearly 5-fold increase is not statistically significant, it appears that in a larger sample size, significance would be reached. This is the first study reported that examined the correlation of NPSLE manifestations with anti-infectious Abs.

Altman A, Szyper-Kravitz M, Shoenfeld Y. · Center for Autoimmune Diseases and Department of Medicine B, Sheba Tel-Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Rheumatol Int. · Pubmed #18034245 No free full text.

Abstract: The etiology of dermatomyositis is unknown, but immune mechanisms play an important role. Several dermatological manifestations have been reported among carriers of hepatitis B surface antigen, and after vaccination with the HBV vaccine. Almost all the skin reactions described were peculiar skin eruptions suggestive of an immune complex reaction. Some authors described the occurrence of dermatomyositis after BCG and influenza vaccination. We report a case of a 6-year-old child, who was vaccinated for hepatitis B virus and developed a flu-like disease accompanied by a skin rash, which had the typical features of dermatomyositis. The association of vaccination with autoimmunity is discussed.

Berlin T, Zandman-Goddard G, Blank M, Matthias T, Pfeiffer S, Weis I, Toubi E, Singh S, Asherson R, Fraser A, Gilburd B, Sapir T, Levy Y, Lukac J, Rozman B, Kveder T, Shoenfeld Y. · Department of Medicine E, Meir Hospital, Kfar Saba, Israel. · Ann N Y Acad Sci. · Pubmed #17894023 No free full text.

Abstract: Infections can act as environmental triggers inducing or promoting autoimmune disease in genetically predisposed individuals. Identification of microbial peptides similar to self-tissues may by molecular mimicry, provide the inducing mechanism for an immune response. The aim of this study was to identify autoantibodies (autoAbs) in nonautoimmune individuals during acute bacterial, viral, or parasitic infections. Specific Abs or specific infections with an increased autoAb load may shed insight into the mechanisms of autoimmune disease. Sera from 88 patients with acute infections (41 bacterial, 23 viral, 17 parasitic, and 7 rickettsial) were tested by the ELISA method for antinuclear antibodies (ANA) 8 Pro, and Abs to thyroid peroxidase (TPO), thyroglobulin, phospholipids, annexin-V, laminin, anti-Saccharomyces cervisiae (ASCA), and prothrombin, along with 80 normal controls. Elevated titers of Abs to annexin-V and prothrombin were the most prevalent in viral, parasitic, and rickettsial infections and to laminin in viral and parasitic infections. Elevated titers of ASCA and ANA were found in viral and bacterial infections. Antiphospholipid Abs were found in parasitic and Q-fever infections. Thirty-four individuals harbored elevated titers of at least two Abs. An autoAb burden was detected in individuals with hepatitis A, hepatitis B, toxoplasma or Q-fever infections. In nonautoimmune individuals with various (bacterial, viral, parasitic, and rickettsial) infections, elevated titers of Abs to annexin-V, prothrombin, laminin, ASCA, ANA, and phospholipids were most frequently detected.

Mondini M, Vidali M, De Andrea M, Azzimonti B, Airò P, D'Ambrosio R, Riboldi P, Meroni PL, Albano E, Shoenfeld Y, Gariglio M, Landolfo S. · Medical School of Turin, Turin, and Medical School of Piemonte Orientale, Novara, Italy. · Arthritis Rheum. · Pubmed #17133607 links to  free full text

Abstract: OBJECTIVE: To investigate the presence and clinical significance of autoantibodies against the interferon-inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases. METHODS: Immunohistochemical analysis was used to evaluate the expression of IFI16 in skin biopsy specimens obtained from patients with SSc and patients with SLE. Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme-linked immunosorbent assay. Other autoimmune diseases such as primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), chronic urticaria, and hepatitis C virus (HCV) infection were also examined. RESULTS: Expression of IFI16 was greatly increased and was ubiquitous in all layers of the epidermis and in the dermal inflammatory infiltrates of lesional skin from both patients with SLE and patients with SSc. Patients with SLE, those with primary SS, and those with SSc exhibited significantly higher anti-IFI16 IgG antibody levels compared with normal controls (for SLE, P < 0.002; for primary SS, P < 0.001; for SSc, P < 0.0005). Anti-IFI16 titers above the ninety-fifth percentile for control subjects were observed in 26% of the patients with SLE, 50% of those with primary SS, and 21% of those with SSc (28% of patients with limited cutaneous SSc [lcSSc] versus 4% of patients with diffuse cutaneous SSc [dcSSc]). In contrast, the prevalence of anti-IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection. CONCLUSION: The results of this study provide evidence that an IFN-inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc. Moreover, a strict correlation with lcSSc was also demonstrated, thus providing a novel tool in the differential diagnosis of lcSSc from dcSSc.

Toubi E, Gordon S, Kessel A, Rosner I, Rozenbaum M, Shoenfeld Y, Zuckerman E. · Division of Clinical Immunology and Allergy, Bnai-Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel. · J Autoimmun. · Pubmed #17029886 No free full text.

Abstract: In this study we aimed to determine whether serum B-lymphocyte activating factor (BAFF) level is increased in patients with chronic hepatitis C virus (HCV) infection, and to assess its association with HCV-related autoimmunity. Sixty-five patients with chronic HCV infection were compared with two disease control groups [57 patients with systemic lupus erythematosus (SLE) and 15 with chronic hepatitis B virus (HBV) infection] and a healthy control group of 35 individuals. A special attention was given to HCV-related arthralgia and or vasculitis. Serum BAFF was assessed in all studied individuals, whereas rheumatoid factor (RF), anti-cardiolipin antibodies (aCL), and cryoglobulins were determined in HCV and HBV infected patients, and anti-dsDNA antibodies and aCL were assessed in patients with SLE. Mean serum BAFF was increased in patients with HCV infection and SLE (2.4+/-0.8 ng/ml and 3.1+/-1.34 ng/ml respectively) compared to 1.1+/-0.14 ng/ml in patients with HBV; and to 1.1+/-0.27 in healthy controls (all, p<0.0001). The elevation in serum BAFF was associated with HCV-related arthralgia and or vasculitis (p<0.0001), and with the presence of aCL and of cryoglobulins. HBV patients lacked features suggestive of autoimmunity. In SLE patients, elevated serum BAFF was in association with the presence of anti-dsDNA (p=0.002). As in other autoimmune diseases, increased serum BAFF was also found in patients with chronic HCV infection. Elevated serum BAFF levels were associated with clinical and laboratory features of autoimmunity, suggesting that BAFF may play a role in HCV-related autoimmunity.

Levy Y, Uziel Y, Zandman G, Rotman P, Amital H, Sherer Y, Langevitz P, Goldman B, Shoenfeld Y. · Department of Medicine E, Meir Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Ann N Y Acad Sci. · Pubmed #16127015 No free full text.

Abstract: Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it responds to corticosteroids therapy, but in certain cases it may resist corticosteroid or immunosuppressive treatment, or both. The objective of this study is to present case reports of patients who exhibited various inflammatory diseases, accompanied with vasculitic peripheral neuropathies, for which intravenous immunoglobulin (IVIg) was used for treatment. The study included 10 patients with the following: Sjögren's syndrome (1), systemic lupus erythematosus (2), vaccination-induced vasculitis (1), Churg-Strauss vasculitis (1), mixed cryoglobulinemia (2), polyarteritis nodosa (1), sarcoidosis (1), and scleroderma (1). All developed vasculitic peripheral neuropathy and were treated with 1-13 cycles of high-dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. Results showed that in all but two patients (mixed cryoglobulinemia associated with hepatitis C and sarcoidosis), neuropathy improved or completely resolved after IVIg treatment. In conclusion, IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment in patients for whom conventional treatment is contraindicated, or for patients in whom conventional treatment has failed.