SUMMARYThe frequency and specificity of antibodies to native and denatured coUagens were evaluated in systemic sclerosis (SSc) and in primary Raynaud's phenomenon (PRP) by direct and competitive ELISA. Antibodies reactive with denatured collagen type I (CI) were found in 43% of the SSc sera, and anti-CIV and anti-CV in 31%. In PRP, anti-CI, anti-CIV and anti-CV antibodies were detected in 8% of patient sera. Anti-CI, anti-CIV and anti-CV antibodies reacted with determinants expressed on the native as well as on the denatured molecule. Anti-CI and anti-CIV were cross-reactive; a reactivity with CII and a lower one with CV were detected. Anti-CV antibodies also reacted with CI and CII and, in a smaller proportion of cases, with CIV. Anti-collagen antibodies, affinity-purified from blotted collagen IV and V and cyanogen bromide (CBr)-digested CI, displayed the cross-reactivities shown by inhibition studies on sera. Moreover, antibodies eluted from a CBr fragment of CI reacted with the other CBr fragments as well. These data show that one-third of SSc sera contain antibodies that react with epitopes expressed on native as well as on heat-denatured CI, CII, CIV and CV, and therefore have the potential to bind collagens in vivo.

SUMMARYMixed cryoglobutinaemia (MC) is a disorder eharaclerized by the presence of large amounts of cryoprecipitating fgM-lgG complexes. An immune complex glomerulonephritis develops in one third of all patients, but its occurrence docs not seem related lo the amount ofcryoglobulins in the sera, nor to their complement-fixing ability. In this study we investigated the presence of IgG antibodies reactive with kidney antigens in 33 MC patients {11 with glomerulonephritis, 22 without renal involvement). A total glomerular extract was run on a 10''^. acrylamidc gel, blotted to nitrocellulose and probed with the patients' sera. Sera from half of the palients without renal involvement reacted with several glomerular antigens whose molecular weight ranged between 200 and 29 kD. In the group with renal involvement, sera from 7/11 patients reacted with an antigen of 50 kD, which is also expressed in thymus. but not in the heart or liver. In a follow-up study of four patients with renal involvement, lhe amount of serum antibody specific for the 50-kD antigen fiuctuated, cither spontaneously or in respon.se to therapy. These results show that antibodies specific for glomerular antigens are detectable in MC sera. The immune response againsi a 50-kD antigen expressed in the kidney and thymus seems to be restricted to a subset of MC patients with renal involvement. Circulating autoantibodies specific for glomerular antigens might contribute to the induction of glomerulonephritis in MC forming immune complexes in .situ.

Kidney involvement in immuno-mediated diseases is a life threatening complication to be early detected. Glomerulo-tubular functional indices, kidney-released enzymes and metabolic profiles were assessed in 21 patients with systemic lupus erythematosus, progressive systemic sclerosis and mixed cryoglobulinaemia, without overt nephropathy at a current laboratory examination, and in 31 age-sex-matched healthy controls. All patients had a urinary total protein excretion rate higher than controls (353.6 +/- 182.4 vs 243.0 +/- 108.2 mg/24 h, p < 0.01); 12 of them resulted albuminuric (775.5 +/- 1192.4 mg/24 h), while 9 were normoalbuminuric (16.6 +/- 7.6 mg/24 h). Urinary enzyme excretion rates (GGT and NAG) were significantly heightened compared to healthy subjects, both in albuminuric and in normoalbuminuric patients. Serum albumin resulted significantly lower in all patients, independent of their urinary albumin leakage. Finally, all subjects with connective tissue diseases had significantly higher triglycerides, lower HDL cholesterol and double serum fasting insulin than normals. In conclusion, all patients with collagen diseases show signs of subclinical nephropathy, not always detectable by albuminuria. They also provide evidence of insulin-resistance, a conceivable forerunner of cardiovascular complications.

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