MCTD: a concept which stood the test of time

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; 52: 148–159 .

Sharp GC , Irvin WS , May CM et al. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective tissue disease, systemic lupus erythematosus and other rheumatic diseases . New Engl J Med 1976; 295: 1149–1154 .

Sullivan WD , Hurst DJ , Harmon CE et al. A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease . Medicine (Baltimore) 1984; 63: 92–107 .

Alpert MA , Goldberg SH , Singsen BH et al. Cardiovascular manifestations of mixed connective tissue disease . Circulation 1983; 68: 1182–1193 .

Marshall JB , Kretschmar JM , Gerhardt DC et al. Gastrointestinal manifestations of mixed connective tissue disease . Gastroenterology 1990; 98: 1232–1238 .

Sharp GC , Singsen BH . Mixed connective tissue disease. In: Rose N , Mackay I (eds). The Autoimmune Diseases. Academic Press, Inc.: Orlando , 1985, pp 81–118.

Kasukawa R , Sharp GC . Mixed Connective Tissue Disease and Antinuclear Antibodies. Elsevier: Amsterdam , 1987, pp 23–47.

Sharp GC , Hoffman RW . Overlap syndromes: mixed connective tissue disease and Sjögren's syndrome. In: Lahbita RG (ed). Systemic Lupus Erythematosus, 3rd ed. Academic Press: New York , 1999, pp 551–573.

Porter JF , Kingsland LC III , Lindberg DAB et al. The AI/RHEUM knowledge-based computer consultant system in rheumatology: performance in the diagnosis of 59 connective tissue disease patients from Japan . Arthritis Rheum 1988; 31: 219–226 .

Takano M , Golden SS , Sharp GC , Agris PF . Molecular relationships between two nuclear antigens, ribonucleoprotein and Sm: purification of active antigens and their biochemical characterization . Biochemistry 1981; 21: 5929–5936 .

Lerner MR , Steitz JA . Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus . Proc Natl Acad Sci USA 1979; 76: 5495–5499 .

Pettersson I , Hinterberger M , Mimori T , Gottlieb E , Steitz JA . The structure of mammalian small nuclear ribonucleoproteins: identification of multiple protein components reactive with anti-(U1) ribonucleoprotein and anti-Sm autoantibodies . J Biol Chem 1984; 259: 5907–5914 .

Pettersson I , Wang G , Smith EI et al. The use of immunoblotting and immunoprecipitation of (U) small nuclear ribonucleoproteins in the analysis of sera of patients with mixed connective tissue disease and systemic lupus erythematosus: a cross-sectional, longitudinal study . Arthritis Rheum 1986; 29: 986–996 .

Nyman U , Hallman H , Hadlaczky G , Pettersson I , Sharp G , Ringertz NR . Intranuclear localization of snRNP antigens . J Cell Biol 1986; 102: 137–144 .

Ringertz N , Hadlaczky G , Hallman H , Nyman U , Pettersson I , Sharp GC . Computer analysis of the distribution of nuclear antigens: studies on the spatial and functional organization of the interphase nucleus . J Cell Sci 1986; 4(Suppl): 11–28 .

Takeda Y , Wang GS , Wang RJ et al. Enzyme-linked immunosorbent assay using isolated (U) small nuclear ribonucleoprotein polypeptides as antigens to investigate the clinical significance of autoantibodies to these polypeptides . Clin Immunol Immunopathol 1989; 50: 213–230 .

Takeda Y , Nyman U , Winkler A et al. Antigenic domains on the U1 small nuclear ribonucleoprotein-associated 70K polypeptide: a comparison of regions selectively recognized by human and mouse autoantibodies and by monoclonal antibodies . Clin Immunol Immunopathol 1991; 61: 55–68 .

Hoffman RW , Rettenmaier LJ , Takeda Y et al. Human autoantibodies against the 70 kD polypeptide of U1 small nuclear RNP are associated with HLA-DR4 among connective tissue disease patients . Arthritis Rheum 1990; 33: 666–673 .

Kaneoka H , Hsu K-C , Takeda Y , Sharp GC , Hoffman RW . Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U170 kD autoantibody positive connective tissue disease patients . Arthritis Rheum 1992; 35: 83–94 .

Hoffman RW , Cassidy JT , Takeda Y , Smith-Jones EI , Wang GS , Sharp GC . U1-70 kD autoantibody-positive connective tissue disease in children: a longitudinal clinical and serologic analysis . Arthritis Rheum 1993; 36: 1599–1602 .

Hoffman RW , Sharp GC , Deutscher SL . Analysis of anti-U1 RNA antibodies in patients with connective tissue disease: association with HLA and clinical manifestations of disease . Arthritis Rheum 1995; 38: 1837–1844 .

Hoffman RW , Sharp GC . Is anti-U1-RNP autoantibody positive connective tissue disease genetically distinct? J Rheumatol 1995; 22: 586–589 .

Smolen JS , Steiner G . Mixed connective tissue disease: to be or not to be? Arthritis Rheum 1998; 41: 768–777 .

Burdt MA , Hoffman RW , Deutscher SL , Wang GS , Johnson JC , Sharp GC . Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings . Arthritis Rheum 1999; 42: 899–909 .

Holyst M-M , Hill DL , Hoch SO , Hoffman RW . Analysis of human T cell and B cell responses against U-small nuclear ribonucleoprotein 70 kD, B and D polypeptides among patients with systemic lupus erythematosus and mixed convective tissue disease . Arthritis Rheum 1997; 40: 1493–1503 .

Talken BL , Bailey CW , Reardon SL , Caldwell CW , Hoffman RW . Structural analysis of TCR alpha and beta chains from human T-cell clones specific for small nuclear ribonucleoprotein polypeptides Sm-D, Sm-B and U1-70 kDa: TCR complementarity determining region 3 usage appears highly conserved . Scand J Immunol 2001; 54: 204–210 .

Greidinger EL , Foecking MF , Schäfermeyer KR et al. T cell immunity in connective tissue disease patients targets the RNA binding domain of the U1-70 kD small nuclear ribonucleoproein (submitted for publication).

Greidinger EL , Hoffman RW . The appearance of U1-RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1-70 kD and B0=B proteins as predominant U1-RNP immunogens . Arthritis Rheum 2001; 44: 368–375 .

Greidinger EL , Casciola-Rosen L , Morris SM , Hoffman RW , Rosen A . Autoantibody recognition of distinctly modified forms of the U1-70 kD antigen is associated with different clinical disease manifestations . Arthritis Rheum 2000; 43: 881–888 .