Background Prolidase deficiency is a rare autosomal recessive disease in which one of the last steps of collagen metabolism, cleavage of proline-containing dipeptides, is impaired. Only about 93 patients have been reported with about 10% also having systemic lupus erythematosus (SLE). Methods We studied a large extended Amish pedigree with four prolidase deficiency patients and three heterozygous individuals for lupus-associated autoimmunity. Eight unaffected Amish children served as normal controls. Prolidase genetics and enzyme activity were confirmed. Antinuclear antibodies (ANA) were determined using indirect immunofluorescence and antibodies against extractable nuclear antigens were determined by various methods, including double immunodiffusion, immunoprecipitation and multiplex bead assay. Serum C1q levels were determined by enzyme-linked immunosorbent assay. Results Two of the four homozygous prolidase deficiency subjects had a positive ANA. One had anti-double-stranded DNA, while another had precipitating anti-Ro. By the simultaneous microbead assay, three of the four had anti-Sm and anti-chromatin. One of the three heterozygous subjects had a positive ANA and immunoprecipitation of a 75 000 molecular weight protein. The unaffected controls had normal prolidase activity and were negative for autoantibodies. Conclusions Prolidase deficiency may be associated with the loss of immune tolerance to lupus-associated autoantigens even without clinical SLE.

Genetic complete deficiency of the early complement components such as C1, C2 and C4 commonly results in a monogenetic form of systemic lupus erythematosus (SLE). However, previous studies have examined groups of complete complement deficient subjects for SLE, while a familial SLE cohort has not been studied for deficiencies of complement. Thus, we undertook the present study to determine the frequency of hereditary complete complement deficiencies among families with two or more SLE patients. All SLE patients from 544 such families had CH50 determined. Medical records were examined for past CH50 values. There were 66 individuals in whom all available CH50 values were zero. All but four of these had an SLE-affected relative with a non-zero CH50; thus, these families did not have monogenic complement deficient related SLE. The four remaining SLEaffected subjects were in fact two sets of siblings in which 3 of the 4 SLE patients had onset of disease at <18 years of age. Both patients in one of these families had been determined to have C4 deficiency, while the other family had no clinical diagnosis of complement deficiency. In this second family, one of the SLE patients had had normal C4 and C3 values, indicating that either C1q or C2 deficiency was possible. Thus, only 2 of 544 SLE families had definite or possible complement deficiency; however, 1 of 7 families in which all SLE patients had pediatric onset and 2 of 85 families with at least 1 pediatric-onset SLE patent had complete complement deficiency. SLE is found commonly among families with hereditary complement deficiency but the reverse is not true. Complete complement deficiency is rare among families with two or more SLE patients, but is concentrated among families with onset of SLE prior to age 18.

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