Antibody‐Secreting Cell Specificity in Labial Salivary Glands Reflects the Clinical Presentation and Serology in Patients With Sjögren's Syndrome

Maier-Moore, Jacen S.; Koelsch, Kristi A.; Smith, Kenneth; Lessard, Christopher J.; Radfar, Lida; Lewis, David M.; Kurien, Biji T.; Wolska, Nina; Deshmukh, Umesh S.; Rasmussen, Astrid; Sivils, Kathy L.; James, Judith A.; Farris, A. Darise; Scofield, R. Hal

doi:10.1002/art.38872

Cited by 34 publications

(31 citation statements)

References 36 publications

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“…These studies showed the autoantibody repertoire of the monoclonal antibodies produced from a given subject reflected the antibodies found in the peripheral blood. Thus, this study confirms that the salivary glands are a site for the production of autoantibodies in Sjögren’s (35). The peripheral proteomic study and the salivary gland monoclonal antibody study have not determined the extent to which salivary autoantibody production contributes to circulating anti-Ro60, however.…”

Section: Autoantibodies Precede Diseasesupporting

confidence: 84%

“…Thus, anti-Ro60 was produced by short lived B cells with rapid turnover (34). Maier-Moore and colleagues (35) produced recombinant monoclonal antibody from antibody-producing B cells infiltrating the salivary glands of Sjögren’s patients. These studies showed the autoantibody repertoire of the monoclonal antibodies produced from a given subject reflected the antibodies found in the peripheral blood.…”

Section: Autoantibodies Precede Diseasementioning

confidence: 99%

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Autoantibodies in Sjögren’s Syndrome

Fayyaz

Kurien

Scofield

2016

Rheumatic Disease Clinics of North America

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171

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Our purpose was to compile information on antibodies in Sjögren’s syndrome, focusing more on clinical manifestations associated with anti-Ro/SSA and anti-La/SSB antibodies and studies regarding novel antibodies. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading Sjogren’s in combination with antibodies and congenital heart block (CHB). Almost half of asymptomatic mothers giving birth to children with CHB ultimately develop Sjögren’s. We have discussed studies concerning the presence of antibodies predating clinical manifestations of disease. We have considered, in addition to anti-Ro/SSA and anti-La/SSB, anti-centromere antibody (ACA), anti-mitochondrial antibody (AMA) and many novel autoantibodies that have been analyzed in the literature. Studies in the future are required to ascertain the pathogenic mechanisms associated with these antibodies and the specific clinical manifestation related to new autoantibodies.

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Section: Autoantibodies Precede Diseasesupporting

confidence: 84%

Section: Autoantibodies Precede Diseasementioning

confidence: 99%

Autoantibodies in Sjögren’s Syndrome

Fayyaz

Kurien

Scofield

2016

Rheumatic Disease Clinics of North America

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171

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“…Biopsy tissue was mechanically separated and enzymatically digested as previously described (49). PB mononuclear cells were isolated from fresh blood samples using density-gradient centrifugation (Ficoll-Paque; GE Healthcare Life Sciences).…”

Section: Methodsmentioning

confidence: 99%

Single-cell analysis of glandular T cell receptors in Sjögren’s syndrome

Joachims¹,

Leehan²,

Lawrence³

et al. 2016

JCI Insight

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CD4+ T cells predominate in salivary gland (SG) inflammatory lesions in Sjögren’s syndrome (SS). However, their antigen specificity, degree of clonal expansion, and relationship to clinical disease features remain unknown. We used multiplex reverse-transcriptase PCR to amplify paired T cell receptor α (TCRα) and β transcripts of single CD4+CD45RA− T cells from SG and peripheral blood (PB) of 10 individuals with primary SS, 9 of whom shared the HLA DR3/DQ2 risk haplotype. TCRα and β sequences were obtained from a median of 91 SG and 107 PB cells per subject. The degree of clonal expansion and frequency of cells expressing two productively rearranged α genes were increased in SG versus PB. Expanded clones from SG exhibited complementary-determining region 3 (CDR3) sequence similarity both within and among subjects, suggesting antigenic selection and shared antigen recognition. CDR3 similarities were shared among expanded clones from individuals discordant for canonical Ro and La autoantibodies, suggesting recognition of alternative SG antigen(s). The extent of SG clonal expansion correlated with reduced saliva production and increased SG fibrosis, linking expanded SG T cells with glandular dysfunction. Knowledge of paired TCRα and β sequences enables further work toward identification of target antigens and development of novel therapies.

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“…Among other roles, α-enolase has been reported as an allergenic molecule with immune and strong pro-inflammatory properties [69][70][71] . In rats, high expression of α-enolase has been associated with increased numbers of CD4+ T cells and immuno rejection in an allograft transplantation model 72 .…”

Section: Molecular Biosystems Accepted Manuscriptmentioning

confidence: 99%