Session Type: Abstract Submissions (ACR)
Myositis-specific antibodies have been proposed as tools for disease classification as they are correlated with certain clinical and genetic features. Recently, two new DM-specific autoantigens have been described—TIF-g and NXP-2. Detection of autoantibodies to these proteins has largely been assayed by immunoprecipitation from radiolabeled cell lysates, and thus may not have characterized the patients’ immune responses with maximal sensitivity and specificity. We hypothesized that development of sensitive assays for detection of these specificities would enable us to see different patterns of skin and systemic disease associated with these antibodies when applied prospectively to a large DM cohort.
We designed, optimized and validated novel, sensitive, and highly specific assays to detect antibodies against TIF-g and NXP-2. To detect TIF-g antibodies, HeLa cells were transiently transfected with the appropriate cDNA, resulting in expression levels 33-62 fold above endogenous levels. Immunoprecipitations were performed using these transfected lysates, electrophoresed on SDS-polyacrylamide gels, transferred to nitrocellulose and immunoblotted with an anti-TIF-g monoclonal antibody. NXP-2 antibodies were assayed by immunoprecipitation using 35S-methionine labeled NXP-2 generated by in vitro transcription-translation as source material. Patient sera from a large DM cohort at the Stanford University Dermatology Outpatient Clinic (n = 111) were tested for antibodies against TIF-g and NXP-2 using these assays. In order to maximize stringency and clinical utility, we compared the features of patients with a specific autoantibody to those without the antibody (as opposed to those with another antibody). Dichotomous variables were evaluated using Fisher exact tests. We used unpaired t tests (two-tailed) to evaluate differences between continuous variables.
Antibodies to TIF-g and NXP-2 were detected in 37% and 14% of patients, respectively. When compared to those without antibodies to TIF-g, anti-TIF-g patients were associated with female sex, positive ANA, absence of arthralgia, “V” sign, and difficulty with controlling skin inflammation. Antibodies to NXP-2 were associated with male sex, internal malignancy, calcinosis cutis, absence of alopecia/ulceration/Gottron’s papules/elbow and knee rash, positive response to hydroxychloroquine, and satisfactory control of skin disease. In the non-amyopathic subgroup, patients with antibodies to TIF-g were significantly associated with lower maximal CK values than those without (488 vs 3467, respectively, p=0.05).
Over 50% of our Stanford DM cohort can be typed by antibodies to either NXP-2 or TIF-g. NXP-2 antibodies are associated with calcinosis cutis, malignancy, and a benign course of skin disease, while TIF-g antibodies are characterized by absence of arthralgia, “V” sign, relatively low CK values, and skin inflammation that is difficult to control.
Gilead and Actelion,
Gilead, Actelion, Pfizer, United Therapeutics,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-responses-to-nxp-2-and-tif-g-are-associated-with-distinct-clinical-phenotypes-and-prognosis-for-skin-disease-in-dermatomyositis-patients/