High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor   inhibitors in rheumatoid arthritis

Bobbio-Pallavicini, Francesca; Caporali, Roberto; Alpini, Claudia; Avalle, Stefano; Epis, Oscar Massimiliano; Klersy, Catherine; Montecucco, Carlomaurizio

doi:10.1136/ard.2006.060608

Cited by 120 publications

(98 citation statements)

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“…Recently, anti-citrullinated protein antibodies (ACPAs) have been shown to be more specific for RA (2). The presence of RF and ACPA autoantibodies is associated with disease progression (3) and responsiveness to treatment with antirheumatic drugs (4,5). Also, animal studies have shown that B cells are necessary for the development of arthritis and influence its severity (6).…”

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confidence: 99%

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Teng

Levarht

Hashemi

et al. 2007

Arthritis & Rheumatism

167

113

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Objective. Anti-CD20-mediated B cell depletion with rituximab is a new and effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral blood (PB) are consistently depleted in all patients, the clinical effects are more heterogeneous, possibly related to differences in the depleting effects of lymphoid or solid tissues. The aim of this study was to investigate B cell depletion in different compartments (PB, bone marrow, and synovium) and determine predictive variables for responsiveness to rituximab therapy.Methods. Before and 12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were collected from 25 patients with RA refractory to disease-modifying antirheumatic drugs and tumor necrosis factor-blocking agents. CD19؉ and CD20؉ B cells in PB and bone marrow were measured by flow cytometric analysis, whereas CD79a؉ and cytoplasmic CD20؉ B cells in the synovium were stained by immunohistochemistry. The effects of rituximab on serum Ig and autoantibodies were measured by enzyme-linked immunosorbent assay.Results. Rituximab effectively depleted the CD20؉ subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab significantly reduced autoantibody production (anti-citrullinated pro- Conclusion. These data provide novel insights into the mechanisms of CD20-mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.

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confidence: 99%

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Teng

Levarht

Hashemi

et al. 2007

Arthritis & Rheumatism

167

113

View full text Add to dashboard Cite

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“…Therefore the increased severity of disease associated with the presence of RF IgA seems not to be attributable to these cytokines [33,34]. Accordingly, no correlation was found between serum IL-6 or BLyS levels and the levels of total or IgA-specific RF.…”

Section: Discussionmentioning

confidence: 90%

“…Evidence in the literature indicates that people with RA positive for RF IgA show more aggressive disease [33,34]. Furthermore, RF IgA seems to have a greater role in predicting the development of RA than RF IgM.…”

Section: Discussionmentioning

confidence: 99%

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Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

Fabris¹,

Vita

Blasone³

et al. 2010

Autoimmun Highlights

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at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine, chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month +6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation, interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a-CCP, nor RF IgA compared to routine total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.

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“…Consistent with our findings implicating IgA RF more than IgM RF, Mikuls et al [36] found an association between CS and high serum IgA RF but not IgM RF in African Americans with RA. It has been shown in RA that high pretreatment levels of IgA RF are associated with a poor response to TNF inhibitors [37] and it has also been shown that smokers are poor responders to TNF inhibitors [38], thus, it is likely that the IgA RF link to smoking is the explanation for the former. Since our studies show a correlation between IgA RF and LD, this may also be a marker of relevance to follow in smokers.…”

Section: Discussionmentioning

confidence: 99%

Chronic smoke exposure induces rheumatoid factor and anti‐heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease

et al. 2012

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The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on autoantibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti-cyclic citrullinated peptides (CCPs), and anti-HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking-induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti-HSP70 autoantibodies were identified in CS-exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti-HSP70 IgM, smoke exposure promoted the switch to anti-HSP70 IgG autoantibodies. Elevated anti-CCP autoantibodies were not detected in CS-exposed mice or smokers. AKR/J splenocytes stimulated in vitro by immune complexes (ICs) of HSP70/anti-HSP70 antibodies produced RFs. The CD91 scavenger pathway was required as anti-CD91 blocked the HSP70-IC-induced RF response. Blocking Toll-like receptors did not influence the HSP70-IC-induced RFs. These studies identify both anti-HSP70 and RFs as serological markers of smoke-related LD in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS, in a number of different disease settings.Keywords: Autoantibodies r Heat shock protein 70 r Lung disease r Rheumatoid factor IntroductionSmoking is a very strong environmental risk factor that is linked to rheumatoid arthritis (RA) [1,2] and other autoimmune disCorrespondence: Dr. Marianna M. Newkirk e-mail: Marianna.newkirk@mcgill.ca eases [3][4][5]. Furthermore, there is little information on the association between the most common smoke-induced lung disease (LD), chronic obstructive pulmonary disease (COPD), and serological markers associated with autoimmunity.In North American Native (NAN) populations the prevalence of RA can be three times that of Caucasians [6]. Whereas smoking rates have decreased in the past decade in Caucasians, with 18% of Canadians >15 years of age smoking, 60-70% C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu1052 Marianna M. Newkirk et al. Eur. J. Immunol. 2012. 42: 1051-1061 of NANs (residing mostly on reservations) smoke (Health Canada). Although smoking cessation can lower RA risk and disease burden, the risk continues 10 years after cessation [1] and similarly, prolonged smoking cessation is critical for the reduction of lung cancer [7]. Lung inflammation, oxidative stress, and protease burden remain elevated for several months after smoking cessation [8]. Early diagnosis of those at risk of smoking-related diseases ideally by the use of informative biomarkers is critical with sustained cessation an important goal. Rheumatoid factor (RF), used in the diagnosis of RA [9], is an autoantibody of any isotype that binds IgG Fc. Epidemiological studies have shown that RF-positive RA patients are most associated with an increased risk conferred f...

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High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor inhibitors in rheumatoid arthritis

Abstract: According to the clinical response, anti-TNFalpha agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFalpha inhibitors.

Cited by 120 publications

References 41 publications

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

Chronic smoke exposure induces rheumatoid factor and anti‐heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease

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