Peter S. Friend

Deficiency of the Second Component of Complement (C2) with Chronic Vasculitis

A patient had complete deficiency of the second component of complement associated with chronic vasculitis and increased susceptibility to infection. We discuss here results of the complement profile, histocompatibility typing, and studies of the functional properties of patient plasma or serum in chemotaxis and opsonization in relation to the disease entity and host susceptibility to infection.

C2 deficiency in man. genetic relationship to a mixed lymphocyte reaction determinant (7a

Three unrelated individuals with, respectively, lupus erythematosus, polyarteritis, and membranoproliferative glomerulonephritis and totally deficient in the second component of complement are demonstrated to be mutually poorly reactive in mixed lymphocyte culture and homozygous for the mixed lymphocyte reaction determinant (MLR-S or LD) short 7a (7a*). The gene controlling the elaboration of C2 in man is shown to be separate from, and probably to map outside of, the second locus ofHL-A and theMLR-S locus. Genetic linkage disequilibrium is strongly suggested between HL-A 10, W18, 7a*, and C2 deficiency.

Pathogenesis of membranous nephropathy in systemic lupus erythematosus: possible role of nonprecipitating DNA antibody.

The biological importance of qualitatively different subpopulations of antibody in determining the inflammatory consequence of circulating immune complexes in animal models of chronic serum sickness and human systemic lupus crythematosus (SLE) is wvell recognised. The precise role of antibody precipitability, however, is unclear since numerous investigations have shown seemingly conflicting results. We undertook a study to evaluate thc amount and character of antibody to native DNA in untrcatcd patients with SLE alone or SLE with membranous nephropathy or diffuse proliferative glomerulonephritis.

Inherited deficiency of the second component of complement (C2) with membranoproliferative glomerulonephritis

The occurrence of membranoproliferative glomerulonephritis in a 13 year old boy with inherited complete deficiency of the second component of complement (C2) is described here for the first time. Results of the complement studies and the associations of glomerulonephritis with complement deficiencies are discussed.

Membranous transformation of lupus nephritis

Abstract Transformation from proliferative lupus nephritis to membranous nephropathy with the appearance of nephrotic syndrome was observed after 30 months of aggressive corticosteroid therapy. During this period, levels of serum complement and of circulating immune complexes had returned to normal and the character of native DNA antibody had changed from largely precipitating to nonprecipitating. These findings suggest that the change in antibody response induced by corticosteroid therapy favored the development of membranous nephropathy.

Hypothesis: Immunologic rationale for the therapy of membranous lupus nephropathy☆

Abstract Membranous nephropathy in lupus erythematosus is associated with low titers of nonprecipitating antibody to native DNA in contrast to other forms of lupus nephritis where large amounts of precipitating antibody are found. It is hypothesized that host antibody response determines the nature of the immune complex and hence the location of its deposition in the glomerulus. In addition, since effective immunosuppressive therapy of proliferative glomerulonephritis ultimately leads to disappearance of precipitating antibody and the development of an antibody profile similar to that seen in virginal membranous nephropathy, one possible rational therapy of the latter disease may be no treatment at all. This hypothesis is supported by clinical therapeutic trials insofar as the DNA antibody profiles; however, it is recognized that steroids and/or immunosuppressants may have therapeutic consequences other than those changing the type of immune complexes formed.