Barbara Marchini

Anti-collagen antibodies in systemic sclerosis and in primary Raynaud's phenomenon

The frequency and specificity of antibodies to native and denatured collagens were evaluated in systemic sclerosis (SSc) and in primary Raynauds 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.

Autoantibodies from mixed cryoglobulinaemia patients bind glomerular antigens

Mixed cryoglobulinaemia (MC) is a disorder characterized by the presence of large amounts of cryoprecipitating IgM‐IgG complexes. An immune complex glomerulonephritis develops in one third of all patients, but its occurrence docs not seem related to the amount of cryoglobulins 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% acrylamide gel, blotted to nitrocellulose and probed with the patients’sera. Sera from half of the patients 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, the amount of serum antibody specific for the 50‐kD antigen fluctuated, either spontaneously or in response to therapy. These results show that antibodies specific for glomerular antigens are detectable in MC sera. The immune response against 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.

Molecular mimicry as a mechanism of induction of autoantibodies

Antibodies against small nuclear ribonucleoproteins (snRNP) are frequently produced in systemic autoimmune disorders and different mechanisms have been proposed to account for their production. Molecular mimicry is a well-established phenomenon which can involve exogenous antigens as well as autoantigens. An example of an exogenous antigen, i.e. a viral protein, was reported by Guldner et al. (1990). A 5-amino acid sequence of the p68 protein, a component of U1 snRNP, is shared with the matrix protein of the influenza B virus. A subset of patients with autoimmune disorders, whose sera contain anti-p68 antibodies, react with this shared sequence and with the entire matrix protein. The same p68 protein bears in another region a strong sequence-homology with the third complementarity-determining region (CDR3) of an immunoglobulin light chain. Immunization of normal animals with the light chain induces the production of anti-p68 antibodies (Puccetti et al, 1990). In this case, the sequence mimicking the ribonucleoprotein is contained in the variable region of the immunoglobulin, where the idiotope is located.