Date: Monday, October 22, 2018
Session Title: Sjögren's Syndrome – Basic and Clinical Science Poster
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
There is evidence for B cell involvement in the pathogenesis of Sjögren’s syndrome by the presence of autoantigen-specific B cells. Autoantibodies toward Ro/SSA and La/SSB are classification criteria. Autoantibodies are produced by plasmablasts within the salivary glands, but whether the serum autoantibodies originate from these cells is unknown. We hypothesized that if serum autoantibodies originate from the antibody secreting cells in the glands, they may be present in the saliva prior to their detectable levels in the plasma. As a first step to explore this, we tested the saliva autoantibody profiles in a group of SS patients and sicca controls and compared them to their respective IgG serum autoantibody profiles.
27 subjects, symptomatic for dry eyes and mouth, were evaluated for American/European Consensus Group (AECG) primary SS inclusion/exclusion criteria. 14 subjects met the AECG primary SS criteria, and 1 also met the ACR criteria for SLE. 13 subjects did not meet the SS classification criteria and served as non-Sjogren’s sicca controls. Serum and stimulated parotid saliva samples were obtained from all subjects. Enzyme-linked immunosorbent assays (ELISAs) were performed by applying saliva (1:20, in duplicate) to antigen-coated (Ro/SSA, La/SSB, Sm, and Sm-RNP) plates and detected using anti-human IgA-, or IgG-alkaline phosphatase and substrate. 4 control subjects negative for all SS inclusion criteria and all other measures were used to establish positive thresholds for each ELISA (mean+5SD). To confirm stringency of this measure, we determined that the Q3+1.5*IQR threshold was similar. mAbs produced from salivary gland plasmablasts from 4 SS and 5 sicca control patients were tested for antigen reactivity. Each subject’s saliva specificities were compared to their mAb and serum specificities measured by DID, ELISA, INNO-LIA, and Bioplex 2200.
In the glands from14 patients, 12 had focal lymphocytic sialadentitis (FLS) and 2 had non-specific chronic inflammation (NSCI). Of the 13 sicca controls, 12 had NSCI, one had FLS, and one was histologically normal. Two sicca controls were seropositive for Ro and seronegative for all other antigens. The SS patients had a wide range of serum specificities for Ro/SSA, La/SSB, Sm, and nRNP. In both the SS patients and sicca controls there were saliva reactivities not detectable in the serum; in SS patients, 5/14 were Ro+, 4/14 La+, 4/14 Sm+ and 3/14 smRNP+, and in sicca controls, 8/13 were Ro+, 6/13 La+, 3/13 Sm+ and 3/13 smRNP+. The mAb specificities from SS patients correlated well with the serum specificities, however the monoclonal antibodies from the sicca controls had specificities for all four antigens not detected in the serum.
These findings suggest that the salivary gland may be a source of SS serum autoantibodies. Future studies will evaluate saliva positive, seronegative subjects longitudinally for development of serum autoantibodies. If this does occur, it would be likely that certain sicca controls would then fulfill the criteria for primary SS classification, suggesting that testing of saliva for autoantibodies may be indicated for prediction of progression to systemic disease.
To cite this abstract in AMA style:Koelsch KA, Cavett J, Smith K, Maier-Moore J, Rasmussen A, Lewis DM, Radfar L, Kurien BT, James JA, Sivils KL, Farris AD, Scofield RH. Autoantibodies Present in Saliva from Sjogren’s Syndrome and Non-Sjogren’s Sicca Patients Are Not Detectible in Serum [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/autoantibodies-present-in-saliva-from-sjogrens-syndrome-and-non-sjogrens-sicca-patients-are-not-detectible-in-serum/. Accessed April 8, 2020.
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