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Acquiring new N-glycosylation sites in variable regions of immunoglobulin genes by somatic hypermutation is a common feature of autoimmune diseases
  1. Annie Visser1,
  2. Nishath Hamza2,
  3. Frans G M Kroese1,
  4. Nicolaas A Bos1
  1. 1Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  2. 2National Genetic Center, Royal Hospital, Muscat, Oman
  1. Correspondence to Prof Nicolaas A Bos, Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical center, Groningen 9712 CP, Netherlands; n.a.bos{at}umcg.nl

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With great interest, we read the contribution of Vergroesen et al that was published recently in Annals of the Rheumatic Diseases.1 In this manuscript, the authors describe the observation that immunoglobulin variable (V) region heavy and light chain transcripts from anti-citrullinated protein antibody (ACPA) IgG-expressing B cells in patients with rheumatic arthritis (RA) contain N-glycosylation sites (Nglycs) acquired by somatic hypermutation, whereas these acquired Nglycs (ac-Nglycs) were absent in tetanus toxoid (TT) specific B cells of healthy individuals. The authors postulate that the introduction of ac-Nglycs generates selective advantages that allow ACPA-expressing B cells to escape from classical selection mechanisms in germinal centres. We agree with the authors that this is an important finding which may have important implications for understanding citrulline-specific immunity in RA.

Here we would like to stress that ac-Nglycs, as a consequence of somatic hypermutation, might be important for RA and for many other rheumatoid and non-rheumatoid autoimmune diseases. We have shown previously2 increased numbers of IgG encoding immunoglobulin variable heavy region gene (IGHV) transcripts with ac-Nglycs derived from B cells and plasma cells residing in the inflamed parotid salivary gland of patients with primary Sjögren’s syndrome (pSS) compared with non-pSS sicca controls (24% vs 6%). Importantly, in pSS the IgG encoding transcripts exhibited …

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