Abstract
IntroductionPatients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.MethodsSerum samples of 134 patients with untreated mycobacterium infections (122 TB, 12 nontuberculous mycobacterium) were tested for antibodies against both the citrullinated (Cit) and the non-citrullinated (Arg) form of 2 cyclic synthetic peptides. In 33 patients, a follow-up sample was tested six months after starting anti-mycobacterial drugs.ResultsA substantial proportion of patients with mycobacterial infections demonstrated antibodies against 0401Cit, 0401Arg, 0722Cit and 0722Arg. Fourteen patients demonstrated anti-0401Cit, 83 anti-0401Arg, 22 anti-0722Cit and 61 anti-0722Arg, while none of these antibodies were detected in the 20 healthy controls. All the patients but one, who were anti-0401Cit and anti-0722Cit positive, demonstrated reactivity against the respective Arg peptide. In the subset of 33 patients with a follow-up test six months after starting treatment, the mean levels of antibodies to 0401Cit, 0401Arg, 0722Cit and 0722Arg significantly decreased after treatment. All the patients who were anti-0401Cit and anti-0722Cit positive turned negative after treatment. The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.ConclusionsACPA may be found in patients with TB. In most of the cases, the reactivity is citrulline independent. A positive cyclic citrullinated peptide (CCP) test in these patients should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.
Highlights
Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA)
It has recently been reported that anti-CCP2 antibodies can be detected in 9% of patients with type 1 autoimmune hepatitis (AIH-1) in the absence of recognizable rheumatoid arthritis overlap, and in some cases with high titres, comparable to those observed in RA [6]
0401Cit and 0401Arg, corresponds to the cfc1-cyc peptide used in the first generation cyclic citrullinated peptide (CCP) test (CCP1) and its arginine-containing equivalent cf0-cyc [11]; the sequence of the second pair, 0722Cit and 0722Arg, is related to a peptide used in the second generation CCP test (CCP2), which is defined in patent EP2071335 [12]
Summary
Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). A group of autoantibodies, anti-citrullinated protein antibodies (ACPA), has been described in patients with rheumatoid arthritis (RA) [1]. It has recently been reported that anti-CCP2 antibodies can be detected in 9% of patients with type 1 autoimmune hepatitis (AIH-1) in the absence of recognizable rheumatoid arthritis overlap, and in some cases with high titres, comparable to those observed in RA [6]. We have reported increased levels of anti-CCP2 in up to 32% of patients with tuberculosis (TB) [8] These patients displayed increased frequency of other autoantibodies such as rheumatoid factor (RF), antinuclear antibodies and others [9]. Kakumanu and collaborators have recently reported that anti-CCP1 antibodies found in TB patients often react to the unmodified arginine-containing peptide as well [10]
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