Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: Clues to disease pathogenesis

Novel autoantibody markers for early and seronegative rheumatoid arthritis

“…This hypothesis is corroborated by a novel view postulated by Crow M. on the pathogenic processes occurring in RA [11]. According to Crow, the activation of the innate immune system, with involvement of synovial cells and possible contribution from the type I interferon system, underlies all RA and constitutes a particular feature of ACCP-negative RA [11]. This hypothesis is supported by the reported genetic association of ACCPnegative RA with the IRF5 gene and by the finding of a thicker synovial lining layer in ACCP-negative RA [34,40].…”

“…This may suggest the presence of a common underlying disease mechanism in ACCPnegative and ACCP-positive RA. This hypothesis is corroborated by a novel view postulated by Crow M. on the pathogenic processes occurring in RA [11]. According to Crow, the activation of the innate immune system, with involvement of synovial cells and possible contribution from the type I interferon system, underlies all RA and constitutes a particular feature of ACCP-negative RA [11].…”

“…This hypothesis is supported by the reported genetic association of ACCPnegative RA with the IRF5 gene and by the finding of a thicker synovial lining layer in ACCP-negative RA [34,40]. Crow postulated that in ACCP-positive RA, this initial activation of the innate immune system would be superimposed with activation of the adaptive immune response with specific targeting of citrullinated proteins leading to the formation of ACCP [11]. This would also explain our finding of the common presence of the identified novel autoantibodies in different RA subtypes.…”

“…Novel autoantibodies that are present in the RA population that is seronegative based on current serological testing, can be of added value to RA diagnostics. Furthermore, as latest research points to a subdivision of the criterion-based disease RA into 2 distinct subsets based on the presence of ACCP, and next to nothing is known about the underlying aetiology of ACCPnegative RA, the identification of disease markers for this RA population will provide more insight into the underlying aetiology and pathogenic mechanisms of this disease subtype [8,9,10,11,12]. The fact that rituximab has up till now been shown to be equally efficient in ACCP-negative and ACCP-positive RA patients indicates the relevance of an autoantibody profiling procedure in this seronegative RA patient subpopulation [13].…”

Interstitial lung diseases in children

“…It is the most common CTD in children, but pulmonary involvement is less frequent than in adults. Genetic and environmental factors seem to be important contributors of disease progression, with influence of sex (more frequent in male), presence of two copies of the HLA-DRB1 "shared epitope" (HLA-DR SE) and anticyclic citrullinated peptide antibody (anti-CCP), and possibly tobacco exposure [106,107]. Almost 50% of patients with RA have specific serologic abnormalities several years before the onset of joint symptoms, and the findings of elevated serum levels of IgM rheumatoid factor or anti-CCP is associated with a high risk for the development of RA [107].…”