Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Primary Sjögren’s syndrome (pSS) is an autoimmune exocrinopathy characterized by chronic inflammation and destruction of the salivary and lacrimal glands. Infiltration of B and T-cells and sometimes plasma cells in the salivary glands as well as the presence of lympho-epithelial lesions are characteristic for pSS. Recent studies showed clinical improvement upon rituximab therapy up to 9 months, enforcing the notion that B cells and to a lesser extent plasma cells are important in the pathogenesis. To further unravel BCR involvement in the development of pSS we characterize B-cell and plasma cell clones in an early stage of parotid gland inflammation.
Objective/1) to compare B cell and plasma cell clonality in patients with pSS and sicca in the absence of an auto-immune disease. 2) To determine isotypes in clones identified and compare these between pSS and sicca.
Methods: Five patients with pSS and 5 patients with complaints of sicca without any auto-immune disease (sicca) were included. All pSS patients fulfilled the AECG criteria for pSS and were antibody (ANA, SSA,SSB, Rf) positive. All sicca patients were antibody negative. Immunohistochemistry stainings were performed on formalin-fixed paraffin embedded sections using antibodies against CD22, CD138, IgA, IgG and IgM and scored semi-quantitatively. mRNA was isolated from all parotid gland biopsies and full-repertoire analysis of the immunoglobulin heavy-chain was performed. All amplified products encode the CDR3, a unique sequence that defines a unique clone. The number of sequences reflects the amount of immunoglobulins produced by that clone and can be used as a measure for ‘dominance’ of that particular clone. Of each sample >10,000 BCR sequences were obtained. Clones with a frequency of > 0.5% were arbitrarily considered as dominant clones.
Results: In all patients, almost 3000 clones were recovered (mean 2910 and 2946 and SD 704 and 783 in pSS and sicca resp., p=n.s.) Multiple dominant clones were detected in the parotid gland of all pSS patients (mean 6.2 clones, SD 1.5), only a few dominant clones were detected in the sicca patients (mean 2.4 clones, SD 1.1, p=0.02). Immunohistochemical stainings of the pSS parotid gland biopsies showed that the majority of the infiltrate consisted of B-cells, although a few plasma cells were detectable in all 5 pSS patients. In sicca patients, much less B cells and plasma cells were detectable. Further isotyping revealed that the plasma cells in pSS were mainly expressing IgG (55% IgG, 30% IgA, 15% IgM), while plasma cells from sicca patients were only IgA+ (100% IgA). In line, the highly dominant clones in pSS patients were mainly of the IgG isotype (80% IgG, 16% IgA, 4% IgD), or showing a micture of isotypes, often including IgG. In sicca patients, the very few dominant clones all expressed IgA (100%).
Conclusion: Our observations suggest that the inflamed parotid gland in pSS can be distinguished from sicca based on the expression of IgG by the most dominant B-cell and plasma cell clones. This provides the opportunity to further study the IgG+ B-cell and plasma cell clones in particular for their potential auto-reactive properties. This in turn might lead to understanding of the pathogenesis of pSS and might lead to more targeted therapy.
Disclosure:
M. E. Doorenspleet,
None;
E. Haecke,
None;
P. L. Klarenbeek,
None;
A. Visser,
None;
R. E. Esveldt,
None;
F. Spijkervet,
None;
P. P. Tak,
GlaxoSmithKline,
3;
H. Bootsma,
None;
N. de Vries,
None;
F. Kroese,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-dominant-b-and-plasma-cell-clones-in-patients-with-primary-sjogrens-syndrome-and-patients-with-sicca-syndrome/