Is rheumatoid factor still a superior test for the diagnosis of rheumatoid arthritis?

Abstract

The diagnosis of rheumatoid arthritis (RA) is based primarily on the 1987 revised American College of Rheumatology criteria for RA, which considers mainly the clinical symptoms. But typical clinical symptoms of RA are not manifested completely in early disease course. On the other hand, appreciable advantages have been made in the therapeutic strategy of RA in the last decade and highly effective disease-modifying anti-rheumatic drugs are available now for the control of RA. The treatment strategy for the control of early RA is aggressive. Thus, a highly specific and early diagnostic marker is needed for the detection of RA. Our study is an attempt to see the role of anti-CCP2 antibody (claimed to be highly specific and early diagnostic tool) in the diagnosis of RA. We studied 119 cases of RA in terms of clinical symptoms, disease duration and various autoantibody [including rheumatoid factor (RF), anti-CCP2 antibody, antinuclear antibody, anti-dsDNA] and C-reactive protein status. All the tests were also performed in 26 age and sex-matched healthy controls. Estimation of antibodies was done by quantitative ELISA. IgM RF was positive in 47.89% cases (p value = 0.000), followed by IgG RF (42.01%, p = 0.000) and IgA RF (36.97%, p = 0.000). RF was positive in 64.7% RA cases (p value = 0.000) when all three isotypes were tested together. RF was also detected in one healthy control. In 92 cases, anti-CCP2 Ab was done, hence other data were analyzed further in 92 cases only. Anti-CCP2 Ab was positive (cut-off = 15.0 U/ml) in only 50% RA patients but none of the healthy controls was positive for it. Swelling of joints was seen in 82.6% anti-CCP2 Ab positive cases (p value = 0.092) when compared with anti-CCP2 Ab negative cases (67.4%) while among RF positive cases, only 65.4% ((p value = 0.010) cases had swelling of joints. Out of 39 RA cases presenting with disease duration less than 1 year, only 48.71% patients were anti-CCP2 Ab positive while RF was positive in 61.53% patients. Utility of various combined autoantibody tests revealed that if one does all isotypes of RF (IgG, IgA and IgM) only, then 64.7% RA cases can be diagnosed and if anti-CCP2 Ab is added to it, the sensitivity increases to 75.56%. Thus, our study concludes that anti-CCP2 Ab is not a sensitive test for the diagnosis of RA neither it is useful in early diagnosis of RA, but it increases the sensitivity if added with all RF isotypes.

Blocking Fcα Receptor I on Granulocytes Prevents Tissue Damage Induced by IgA Autoantibodies

“…However, this mechanism may also play an important role in diseases, which are generally not considered as strictly mediated by granulocytes. Rheumatoid arthritis, for instance, is characterized by chronic joint inflammation, in which mononuclear cells like T and B lymphocytes and macrophages play a prominent role (39). Infiltration of granulocytes into the synovial membrane and fluid compartment is, however, also observed.…”

Fine specificity of anti-citrullinated peptide antibodies discloses a heterogeneous antibody population in rheumatoid arthritis

“…Linear citrullinated (Cit) peptides derived from the sequence of human proteins were as follows: PAD 211-30 (VCitVFQATCitGKLSSKCSVVLG) derived from PAD, vim 60-75 (VYATCitSSAVCitLCitSSVP) derived from vimentin, enol [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] (KIHACitEIFDSCitGNPTVE) derived from alpha-enolase, fibrin 617-31 (HSTKCitGHAKSCitPVCitG) derived from the alpha chain of fibrinogen, col-II 358-75 (GACitGLTGCitPGDAGPPGPP) from type II collagen and fillaggrin [SHQEST(Cit)G(Cit)SRGRSGRSG] derived from filaggrin. A non-citrullinated peptide, ctrlPAD (EPLGLQCTFINDFFTYHIRH) derived from PAD was used as control.…”

“…No clinical differences were recorded among SLE and SS patients with and without reactivity against the citrullinated peptides. SLE patients were found positive for antibodies against PAD 211-30 , vim 60-75 , enol [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] , fibrin 617-31 , col-II 358-75 and filaggrin 306-24 in 13·33, 6·67, 1·67, 21·67 and 1·67%, respectively and SS patients in 14·81, 12·96, 7·41, 3·70, 5·56 and 1·85%, respectively. Specificity of antibodies against PAD 211-30 , vim 60-75 , enol [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] , fibrin 617-31 , col-II 358-75 and filaggrin 306-24 among SLE patients ranged from 14·58 to 20·68%, respectively, and for SS patients from 6·67 to 22·75%, respectively.…”

“…The percentages of inhibition of purified anti-peptide antibodies of the two prototype sera after incubation with the homologous peptides were 83·09% for PAD 211-30 , 62·60% for vim 60-75 , 87·15% for enol [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] …”

RF vs. anti-CCP: competitor or companion?

“…by Singh and colleagues [1]. In this article, the authors insisted that the sensitivity of rheumatoid factor (RF) is higher than second-generation anti-cyclic citrullinated peptide (anti-CCP2) test in the diagnosis of rheumatoid arthritis (RA).…”