HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clinical and immunogenetic followup of 46 patients.
OBJECTIVE
To determine any clinical or genetic markers of differentiation and outcome in a previously described cohort of 46 patients with mixed connective tissue disease (MCTD).


METHODS
Patients were clinically evaluated, chart notes reviewed, and HLA subtyping and immunology profiles performed where possible. Eleven had died and 7 were lost to followup.


RESULTS
MCTD had differentiated into systemic lupus erythematosus in 12 patients and into systemic sclerosis in 13. The latter was associated with HLA-DR5 (P = 0.038), and nondifferentiation was associated with HLA-DR2 or DR4 (P = 0.007). Three HLA-DR4 positive patients had MCTD that evolved into rheumatoid arthritis. Erosive and/or deforming arthritis was associated with HLA-DR1 or DR4 (P = 0.015). HLA-DR3 was associated with interstitial lung fibrosis (P = 0.044) and keratoconjunctivitis sicca (0.001 < P < 0.01). Severe Raynaud's phenomenon predicted higher mortality (0.01 < P < 0.05).


CONCLUSIONS
We suggest that MCTD is, for most patients, an intermediate stage in a genetically determined progression to a recognized connective tissue disease. Those whose disease remains undifferentiated might be considered a distinct subset.
Gendi
N S
NS
Nuffield Orthopaedic Centre, Oxford, United Kingdom.
Welsh
K I
KI
Van Venrooij
W J
WJ
Vancheeswaran
R
R
Gilroy
J
J
Black
C M
CM
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000032:analysis; D001168:Arthritis / Q000276:immunology; D002648:Child; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000235:genetics* / Q000276:immunology* / Q000401:mortality
D000974:Antibodies, Antinuclear; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens