Background Sharp described Mixed Connective Tissue Disease (MCTD) in 19721. MCTD is characterised by the presence of Raynaud phenomenon, puffy hands, synovitis, acrosclerosis, myositis and positive anti-ribonucleoprotein (RNP) antibodies. Classification criteria for MCTD except for Kasukawa's criteria demand the presence of high titres of anti-RNP antibodies (measured by hemagglutination). As a result, the cut-point between low and high anti-RNP titres must be well defined. In best of our knowledge, this cut-point have not been established for modern laboratory techniques.
Objectives Determinate a cut-point between low/high anti-RNP titles measured by ELISA, for the diagnosis of Mixed Connective Tissue disease. Describe the clinical and immunological characteristics of patients with positive titres of anti-RNP antibodies.
Methods It was a Retrospective cohort study of patients with positive anti-RNP antibodies (>10) measured by ELISA. We had identified all patients with positive antiRNP antibodies titres in the last five years, using our laboratory base date. Clinical histories were reviewed, we recollected clinical and paraclinical data. We performed descriptive analysis and ROC curves for diagnostic tests with STATA software.
Results We detected 75 patients with positive antiRNP antibodies, we obtained 65 clinical records. 89,23% (58) of patients were women and 10,77% (7) men. The mean age at diagnosis was 45,01 years (SD 16,71 ± years), The median of tracing was seven yeas (P25 de four years/P75 de 14 years). The mean initial antiRNP titre was 239,33 the median was 144 (P25 58/P75 400). The initial diagnosis were Mixed Connective Tissue Disease 6,25% (4), Undifferentiated Connective Tissue Disease 31,25% (20), systemic erythematosus lupus 45,31% (29) and Others 14,06% (9). MCTD diagnosis was made in 29,69% (19) of patients at the end of follow-up. Patients with MCTD as final diagnosis presented in their first visit Raynaud phenomenon 73,68% (14), puffy hands 31,58% (5), acrosclerosis 10,56% (2), myositis 21,05% (4), Arthralgias 68,42% (13), arthritis 57,89% (11), Pulmonary arterial hypertension 5,26% and Interstitial lung disease 10,53% (2). The initial RNP titre was evaluated using the number of times over the laboratory cut point. The area under the ROC curve for the initial RNP was 0,70. Looking for the highest specificity with and adequate sensitivity, we selected the cut-point with highest LR +. The selected cut-point was ≥24,4 times the laboratory cut-point, with s specificity of 77,78 and a sensitivity of 57,89.
Conclusions The cut-point for low/high RNP titres measured by ELISA in our cohort of patients with MCTD as a final diagnosis was ≥24,4 times the laboratory cut-point.
Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR. Mixed connective tissue disease–an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972 Feb;52(2):148–59.
Amigues JM1, Cantagrel A, Abbal M, Mazieres B. Comparative study of 4 diagnosis criteria sets for mixed connective tissue disease in patients with anti-RNP antibodies. Autoimmunity Group of the Hospitals of Toulouse. J Rheumatol. 1996 Dec;23(12):2055–62.
Disclosure of Interest None declared
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