C2 Deficiency DEVELOPMENT OF LUPUS ERYTHEMATOSUS

Abstract

A B S T R A C T The study of serum from a patient with C2 deficiency is described. The patient had an episode of pneumococcal meningitis at 5 mo of age with seizures and transient hemiparesis and apparent purpuric skin lesions. He was first admitted to the University of Minnesota Hospitals at 10 yr of age following the discovery of proteinuria accidentally by his mother. Since then he has been admitted repeatedly to this hospital with numerous clinical findings including arthralgia, recurrent abdominal pain, proteinuria, membranous nephropathy, malar butterfly rash, seizures, personality aberrations, and recurrent fever. In June 1971, the patient developed positive DNA and DNP antibodies and positive LE cells. When the C profile was studied before and after recognition of lupus, Clq, Cls, and C4 dropped. C3 levels were elevated as were C5, C6, and C7. C3 proactivator had been reduced in the patient even before he developed lupus. Also because of a traumatic renal biopsy leading to a perirenal hematoma, he required surgery and a blood transfusion. 1 h after blood transfusion, a C2 titer of 23 hemolytic units was detected. Almost immediately levels of C3, C5, C6, and C7 dropped. C8 and C9 remained elevated. The addition of C2 from normal blood permitted dramatic activation of C3.These findings support the view that the rare deficiency in production of C2 predisposes to serious susceptibility to infection, vascular and mesenchymal disease as well as to renal disease and a lupus syndrome.

Familial discoid lupus erythematosus associated with heterozygote c2 deficiency

“…Low factor B has been noted previously to be associated with C2 deficiency (19), and it is shown that the genes for factor B and C2 are closely linked on the sixth chromosome (20). Our findings regarding factor B are of particular interest in that they suggest two populations of CZdeficient patients4ne with low normal CH50 levels and normal factor B levels, the other with low CH50 levels and low factor B levels.…”

Intraarticular activation of the complement system in patients with juvenile rheumatoid arthritis

“…Four of 8 patients with pauciarticular onset had serum C2 activity selectively depressed to levels observed in individuals heterozygous for C2 deficiency (23). Recent studies have suggested that systemic lupus erythematosus-like disease may develop in patients with homozygous C2 deficiency (47,48), but disease states in relation to heterozygosity have not been thus far noted.…”

Complement genetics, deficiencies, and disease associations

“…Many of these individuals (>60%) do not suffer from any apparent disease, probably due to the compensatory involvement of factor B in the activation of the complement via C2 bypass mechanism (Laich and Sim, 2001). Almost 40% of individuals with C2 deficiency develop systemic autoimmune disease (Agnello et al, 1972;Day et al, 1973;Sjoholm et al, 2006). For instance, systemic lupus erythematosis (SLE) is a disease that presents with facial erythema and oral or nasopharyngeal ulceration.…”