Labial Salivary Gland Antibody-Secreting Cell Specificity and Characteristics in Sjögren’s Patients

Kristi A. Koelsch¹, Jacen Maier-Moore², Kenneth Smith³, Christopher Lessard³, Astrid Rasmussen⁴, Biji Kurien³, Umesh Deshmukh³, A. Darise Farris³, Judith A. James⁵, Kathy L. Sivils⁴, R. Hal Scofield⁶ and Mark Coggeshall⁷, ¹Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Okalahoma City, OK, ²Dept. of Clinical Laboratory Science, University of Texas at El Paso, El Paso, TX, ³Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁴Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁵Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁶US Department of Veterans Affairs Medical Center, Oklahoma City, OK, ⁷Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Antigens, autoantibodies and monoclonal antibodies, Sjogren's syndrome

Session Information

Title: B cell Biology and Targets in Autoimmune Disease: Rheumatoid Arthritis and Related Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose

Studies were approved by the OMRF and the University of Oklahoma Health Sciences Center Institutional Review Boards. Samples and data were obtained from 9 subjects following written, informed consent and evaluated in the OMRF Sjögren’s Research Clinic. Four subjects met American/European combined and American College of Rheumatology criteria for SS. One of these also met the American College of Rheumatology criteria for SLE. Five subjects that did not meet disease criteria served as sicca controls. ASCs were isolated from labial SGs by single-cell-sorting for hmAb production. hmAbs were produced by the OMRF Human Monoclonal Antibody Core. Serum Ab and hmAb profiles of patients and controls were evaluated by various assays to determine specificities including ELISA, immunofluorescence ANA and Crithidia luciliae testing, INNO-LIA™ and BioPlex2200™, and double immunodiffusion (sera only) assays.

Methods

Results

From the 72 hmAbs analyzed to date (52/patient; 20/control), we found diverse antigen specificities, with hmAbs from SS patients more often binding self-antigens. While 56% of the hmAbs from SS patients bound Ro and/or La, only 19% from sicca controls did (p =0.001). We found hmAbs from SS patients to be more often polyreactive (binding more than one antigen) than the controls (29% vs. 12%, respectively). In addition, 3 hmAbs were reactive to the bacterial antigen, peptidoglycan (PGN) (patient = 2, control = 1). The anti-PGN hmAbs also bound common self-antigens. We found correlation between patient serum and SG hmAbs specificities.

Conclusion

In this ongoing study, we show correlations between glandular and serum antibody specificities, demonstrate that ASCs other than anti-Ro or anti-La are present in SS salivary glands and produce Ab in situ. Furthermore, we observed that the SGs are representative of the systemic immune response and that glandular ASC specificities were consistent with co-morbid disease presentation. We have also identified SG derived hmAbs that have cross-reactivity to bacterial- and self-antigens, supporting the theory of an infection-triggering event that leads to development of disease. Finally, these are the first fully human, antigen-specific monoclonal antibodies produced from SS salivary gland ASCs and therefore, may have clinical or diagnostic importance.

Disclosure:

K. A. Koelsch,
None;

J. Maier-Moore,
None;

K. Smith,
None;

C. Lessard,
None;

A. Rasmussen,
None;

B. Kurien,
None;

U. Deshmukh,
None;

A. D. Farris,
None;

J. A. James,
None;

K. L. Sivils,
None;

R. H. Scofield,
None;

M. Coggeshall,
None.

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