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Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate
with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients
with recent-onset rheumatoid arthritis (the Swedish TIRA project)
#MMPMID27859022
Martinsson K
; Johansson A
; Kastbom A
; Skogh T
Clin Exp Immunol
2017[Apr]; 188
(1
): 53-62
PMID27859022
show ga
Given the possible importance of anti-citrullinated peptide/protein antibodies
(ACPA) for initiation and progression of rheumatoid arthritis (RA), extended
knowledge about the different isotypes and subclasses is important. In the
present study, we analysed the immunoglobulin (Ig)G subclasses regarding
reactivity against cyclic citrullinated peptides (anti-CCP) among 504 clinically
well-characterized patients with recent-onset RA in relation to smoking habits,
shared epitope (SE) status and IgA and pan-IgG anti-CCP antibodies. All patients,
regardless of pan-IgG anti-CCP status, were analysed for IgG1-4 CCP reactivity.
Sixty-nine per cent were positive in any IgG anti-CCP subclass, and of these 67%
tested positive regarding IgG1, 35% IgG2, 32% IgG3, and 59% IgG4 anti-CCP. Among
ever-smokers the percentages of IgG2 anti-CCP (P?=?0·01) and IgA anti-CCP
(P?=?0·002)-positive cases were significantly higher compared to never-smokers. A
positive IgG anti-CCP subclass -negative cases. Combining SE and smoking data
revealed that IgG1 and IgG4 anti-CCP were the IgG anti-CCP isotypes associated
with expression of SE, although the lower number of patients positive for IgG2 or
IgG3 anti-CCP could, however, have influenced the results. High levels of IgG2
anti-CCP were shown to correlate with expression of the 'non-SE' allele human
leucocyte antigen (HLA)-DRB1*15. In conclusion, in this study we describe
different risk factor characteristics across the IgG anti-CCP subclasses, where
IgG2 appears similar to IgA anti-CCP regarding the predominant association with
smoking, while IgG1 and IgG4 related more distinctly to the carriage of SE genes.
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