Autoantibody to complement neoantigens in membranoproliferative glomerulonephritis.

With the exception of C3 nephritic factor, autoantibody formation has not been commonly associated with membranoproliferative nephritis (MPGN). We measured autoantibodies (nephritic factors) to the C3 convertases C3bBb (NFa) and C3bBbP (NFt), which result in fast and slow C3 activation, respectively, and to a neoantigen on C1q fixed to a solid phase (spC1q) in sera from 29 patients with MPGN type I, 26 with type II, and 28 with type III. Autoantibody formation was common in all MPGN types. An autoantibody to a C3 convertase neoantigen was identified in more than 75% of the hypocomplementemic MPGN sera tested. Anti-C3bBb (NFa) was present in 81% of patients with MPGN type II but was rarely found in either type I or type III. Anti-C3bBbP (NFt) was common in both MPGN I and III. Anti-spC1q was present in 74% of patients with type I and in 38% and 48% of types II and III MPGN, respectively. Patients with MPGN types I, II, and III had one and two serum autoantibodies detected significantly more frequently than did a group of healthy subjects. The presence of any one autoantibody was not specifically associated with the presence of any other autoantibody. The results indicate that multiple autoantibody formation is common in all MPGN types. MPGN II, and possibly MPGN I, tend to form more specific autoantibodies.

Atypical hypocomplementemic vasculitis syndrome in a child.

We report a patient who developed recurrent urticaria and angioedema at age 2 years, severe hypocomplementemic glomerulonephritis at 11 years, and end-stage renal disease at 14 years. His disease resembled the hypocomplementemic vasculitis syndrome but was atypical in its early age of presentation, severe hypocomplementemia, and progression to end-stage renal disease. Serum C1q levels were extremely low, and C4, C2, C3, and C5 levels were significantly reduced. Serum C1 inhibitor (C1INH) levels were slightly low, presumably from consumption. Circulating C1INH-C1r-C1s complexes were evidenced by reduced ratios of functional to antigenic C1INH and antigenic C1r to C1s. Family members had normal functional and antigenic levels of all complement components studied. The patient's serum, erythrocytes, platelets, and mononuclear cells did not activate complement when mixed with normal target serum. Absence of a circulating complement activator and the low serum C3 and C5 levels suggested the presence of a solid-phase complement activator, possibly related to renal or systemic vascular endothelium. As in patients with homozygous deficiencies of classical pathway components, a severe, prolonged, acquired C1q deficiency may have predisposed this patient to the development of glomerulonephritis.

Idiopathic rapidly progressive glomerulonephritis with C3 nephritic factor and hypocomplementemia.

A 7-year-old boy with mild renal failure and signs and symptoms of acute poststreptococcal glomerulonephritis including severe hypocomplementemia had, by renal biopsy, numerous crescents but no deposits in the glomerular capillary loops. Instead, deposits identical in location and composition to those described for children with idiopathic rapidly progressive glomerulonephritis were present. The severe hypocomplementemia was found to be due to high levels of C3 nephritic factor; niether nephritic factor nor hypocomplementemia has been reported in rapidly progressive glomerulonephritis of the idiopathic type. Following prompt therapy with methylprednisolone intravenously, serologic abnormalities disappeared and renal function greatly improved, but a later biopsy showed 50% of the glomeruli obliterated by scarring. The case is of importance not only in indicating that severe hypocomplementemia does not rule out idiopathic rapidly progressive glomerulonephritis but also in adding to the list of diseases in which nephritic factor can be found.