Selective deficiency of c1s associated with a systemic lupus erythematosus—like syndrome. Report of a case

Abstract

We describe a patient who developed a systemic lupus erythematosus-like syndrome characterized by bilateral malar erythema, antinuclear antibody, and anti-double-stranded DNA antibody. He was started on hemodialysis (3 timedweek) because of renal failure. He completely lacked total hemolytic complement (CH50) activity, which was subsequently determined to be due to the absence of the first component of complement (Cl). The specificity was further defined, by Ouchterlony analysis using anti-Cls antiserum, and was found to be the C1 subcomponent CIS. There was no absence of Clr. We conclude that this is a case of selective deficiency of Cls.Complement deficiency is a rare condition. To date, several cases of complement component deficiency have been reported (I). Of these individuals, some were deficient in C1 because of an absence of one of the C1 subcomponents Clq, Clr, or C l s (2). Until now, however, no patient has been found to be clearly lacking only Cls, although deficiencies of both C l r and C l s have been described (2). It is known that a defect in one of the early components of complement will often induce a systemic lupus erythematosus (SLEtlike syndrome in which there is bilateral malar erythema, positive antinuclear antibody (ANA), and positive anti-double-stranded DNA (anti-dsDNA) antibody (3). We report here a case of selective CIS deficiency in which the subject exhibited an SLE-like syndrome and renal failure. CASE REPORTThe patient, a 26-year-old man, was admitted to our hospital on June 18, 1988 because of orthopnea. Pertinent medical history included removal of his left kidney because of hydronephrosis when he was 3 months old. Data concerning the histologic features of the excised kidney were not available. At age 11, he was diagnosed as having chronic nephritis with proteinuria and hematuria. There was nothing notable in his family's medical history.At the time of admission, the patient was somewhat lethargic and orthopneic. His blood pressure was 133/73 mm Hg, and his pulse rate was 72 beatdminute and regular. He had erythema over the malar region bilaterally. The liver, spleen, and kidney were not palpable; no struma could be felt. There was slight pretibial pitting edema. The palpebral conjunctivae were anemic. No abnormality was detected on neurologic examination. A chest radiograph revealed evidence of previous tuberculosis in the right upper lung field, and an enlarged heart (cardiothoracic ratio 58%). Left ventricular ejection at rest was 14%, as determined by a cardiac pool scintigram, and a myocardial scintigram showed decreased uptake in the apex and anterior front.The total serum protein level was 5.8 g d d l , the blood urea nitrogen and serum creatinine levels were elevated (107 mg/dl and 9.4 mg/ml, respectively), and the creatinine clearance rate was decreased (5.9 mlhinute). He had proteinuria (2.5 grdday), and red blood cells were

Distinct Pathways of Mannan-Binding Lectin (MBL)- and C1-Complex Autoactivation Revealed by Reconstitution of MBL with Recombinant MBL-Associated Serine Protease-2

“…Such analyses await the purification of native MASP-2 to homogeneity for direct comparisons with the recombinant protein. Importantly, our results already indicate that the MASP/MBL pathway of complement activation is qualitatively distinct from the C1 pathway, which is entirely dependent on the presence of both proteases (37,38).…”

Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family

“…In addition to a low level of serum C1s, patient III-1 and her brother patient III-2 showed significantly lower levels of serum C1r. Several previous reports showed that C1s deficiency was sometimes accompanied with C1r deficiency or abnormally low C1r (5,7). In the present study, we screened for abnormalities in the C1r gene, and demonstrated that patient III-1 has no abnormalities, at least in the coding sequence of this gene.…”

“…Several cases of human complement C1 deficiency have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), in which the deficiency was caused by the absence of the subcomponents C1q (6, 9 -13), C1r (3,4,8), C1s (7, 14 -17), or both C1r and C1s (5). The molecular basis for hereditary C1q deficiency is well defined, where homozygosity for nonsense mutations in the C1q A-chain and B-chain genes (6,10,12,13) and deletion, nonsense, and missense mutations in the C1q C-chain gene (10,11) have been demonstrated.…”

Molecular Basis of a Selective C1s Deficiency Associated with Early Onset Multiple Autoimmune Diseases

“…Selective C1s deficiency has been previously reported in only two patients, both from Japan (2,3). Two other different molecular defects were detected in these cases.…”

“…Hereditary deficiency of classical component C2 is the most common deficiency of the complement system in Caucasians, whereas C4 or C1q deficiencies are rare. Only two cases of selective C1s deficiency have been reported to date, both in Japanese patients (1)(2)(3). Human C1s, a 85-kDa glycoprotein, has protease activity and is able to activate the C4 and C2 components of the classical pathway.…”