Response to: ‘Acquiring new N-glycosylation sites in variable regions of immunoglobulin genes by somatic hypermutation is a common feature of autoimmune diseases’ by Visser et al

Vergroesen, Rochelle D; Slot, Linda M.; Hafkenscheid, Lise; Koning, Marvyn T.; Scherer, Hans Ulrich; Toes, René E. M.

doi:10.1136/annrheumdis-2017-212583

Cited by 12 publications

(2 citation statements)

References 4 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B-cell hyperactivity is a hallmark of this disease as, amongst others, revealed by elevated levels of serum IgG and free light chains, presence of rheumatoid factor (RF) and anti-SSA/-SSB autoantibodies, and higher intrinsic levels of Bruton's tyrosine kinase (Btk), an enzyme critically involved in B-cell receptor signaling (1)(2)(3). The B-cell hyperactivity is also illustrated by the presence of clonal expansions of B-cells in labial and parotid glands of pSS patients (4)(5)(6)(7)(8)(9). Chronic activation of B-cells probably also puts pSS patients at a high risk of neoplastic transformation.…”

Section: Introductionmentioning

confidence: 99%

Repertoire Analysis of B-Cells Located in Striated Ducts of Salivary Glands of Patients With Sjögren's Syndrome

et al. 2020

View full text Add to dashboard Cite

A major complication of primary Sjögren's syndrome (pSS) is development of mucosa associated lymphoid tissue (MALT) B-cell lymphoma, particularly in salivary glands. These lymphomas express FcRL4 and are characteristically associated with lymphoepithelial lesions. Neoplastic B-cells may be derived from non-neoplastic glandular intraductal B-cells, also virtually all expressing FcRL4. A characteristic feature of MALT lymphomas is the production of rheumatoid factors (RFs), which are largely encoded by stereotypic immunoglobulin variable heavy chain (IGHV) sequences. The aim of this study was to examine whether there is a relationship between the intraductal and periductal B-cells and whether the intraductal B-cells are selected for RF. RNA was extracted from laser-microdissected infiltrated ductal areas and periductal infiltrates from frozen parotid gland tissue sections of 5 pSS patients. PCR amplified IGHV transcripts were cloned into pCR™4-TOPO vector and subsequently sequenced. Microdissected ducts yielded 96 unique IGHV sequences derived from intraductal B-cells, while 119 unique IGHV sequences were obtained from periductal infiltrates. No major difference in VH-gene usage was observed between intraductal and periductal B-cells. Nearly all (>90%) IGHV sequences derived from both intraductal and periductal B-cells were mutated. Clonal expansions as defined by shared VDJ rearrangements were also present among both intraductal and periductal B-cells: in total 32 clones were found, from which 12 were located within ducts, 15 in periductal areas, and five clones shared members in both areas. We observed 12 IGHV rearrangements encoding for RF sequences from which two were derived from intraductal B-cells and 10 from periductal B-cells. Nine RF sequences were part of a clone. Together these findings indicate that intraductal and periductal B-cells are closely related to each other. Intraductal B-cells are most likely derived from periductal B-cells. We did not obtain evidence that RF-specific B-cells are enriched within the striated ducts. We speculate that in principle any activated B-cell can enter the striated ducts from the periductal infiltrate, irrespective of its antigenic specificity. Within the ducts, these B-cells may receive additional activation and proliferation signals, to further expand at these sites and by acquisition of driver-mutations develop toward lymphoma.

show abstract

Section: Introductionmentioning

confidence: 99%

Repertoire Analysis of B-Cells Located in Striated Ducts of Salivary Glands of Patients With Sjögren's Syndrome

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Long-term observations of RA patients indicate that the ACPA glycosylation process can be detected already more than 15 years before the RA onset and intensifies as the first symptoms of the disease approach [30,31]. The incorporation of N-glycosylation sites is thought to be a result of CD4+ T cell dependent somatic hypermutation of ACPA [32].…”

Section: The Pathogenic Link Between Acpa and Hla In Rheumatoid Arthrmentioning

confidence: 99%

Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis–From Research to Clinical Practice

Wysocki

Olesińska

Paradowska‐Gorycka

2020

Cells

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenic mechanism. However, it has been proven that the key underlying risk factor is a genetic predisposition. Association studies of the HLA-DRB1 gene clearly indicate its importance in RA morbidity. This review presents the current state of knowledge on the impact of HLA-DRB1 gene, functioning both as a component of the patient’s genome and as an environmental risk factor. The impact of known HLA-DRB1 risk variants on the specific structure of the polymorphic HLA-DR molecule, and epitope binding affinity, is presented. The issues of the potential influence of HLA-DRB1 on the occurrence of non-articular disease manifestations and response to treatment are also discussed. A deeper understanding of the role of the HLA-DRB1 gene is essential to explore the complex nature of RA, which is a result of multiple contributing factors, including genetic, epigenetic and environmental factors. It also creates new opportunities to develop modern and personalized forms of therapy.

show abstract

The current status of anti-citrullinated protein antibodies and citrullinated protein-reactive B cells in the pathogenesis of rheumatoid arthritis

Wang

2021

Mol Biol Rep

View full text Add to dashboard Cite

Response to: ‘Acquiring new N-glycosylation sites in variable regions of immunoglobulin genes by somatic hypermutation is a common feature of autoimmune diseases’ by Visser et al

Cited by 12 publications

References 4 publications

Repertoire Analysis of B-Cells Located in Striated Ducts of Salivary Glands of Patients With Sjögren's Syndrome

Repertoire Analysis of B-Cells Located in Striated Ducts of Salivary Glands of Patients With Sjögren's Syndrome

Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis–From Research to Clinical Practice

The current status of anti-citrullinated protein antibodies and citrullinated protein-reactive B cells in the pathogenesis of rheumatoid arthritis

Contact Info

Product

Resources

About