C1r deficiency: an inborn error associated with cutaneous and renal disease

Day, Noorbibi K.; Geiger, Hartmut; Stroud, Robert M.; deBracco, M.; Mancado, B.; Windhorst, Dorothy B.; Good, R. A.

doi:10.1172/jci106902

Cited by 113 publications

(25 citation statements)

References 18 publications

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“…This feature of patients with other genetically determined complement deficiencies and SLE has been observed by others (11,(33)(34)(35) (38). This increased frequency of isolated IgA deficiency in SLE is similar to that for C2, although family studies were not reported for the IgA deficient subjects.…”

Section: Discussionsupporting

confidence: 80%

Inherited deficiency of the second component of complement. Rheumatic disease associations.

Raum²,

et al. 1976

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Section: Discussionsupporting

confidence: 80%

Inherited deficiency of the second component of complement. Rheumatic disease associations.

Raum²,

et al. 1976

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“…Although the function of this pathway is as yet unknown, it has been observed that animals with C4 deficiency and humans with C2 deficiency are relatively free of infection, but patients with nonfunctional C1 have a bactericidal defect and are prone to infection despite an apparent intact alternate complement pathway (7,18,19). Perhaps the repeated infections observed in these patients are secondary to a block in the cytotoxic pathway reported here.…”

Section: Resultsmentioning

confidence: 71%

A New Complement-Mediated Cytolytic Mechanism—the C1-Bypass Activation Pathway

May

Frank

1973

Proc. Natl. Acad. Sci. U.S.A.

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A new cytolytic pathway is described whereby cells sensitized with cytotoxic antibody can be specifically iysed in the complete absence of intact, classical complement pathway function. Evaluation of this model with sera deficient in the 4th (C4), 2nd (C2), and 6th (C6) components of complement has revealed that this new Iytic mechanism, termed the Cl-bypass activation pathway, is initiated by the antibody-mediated activation of C1. Utilizing components of the previously described alternate complement pathway, this pathway bypasses C4 and C2 to activate the third to ninth components of complement (C3-9) with induction of membrane damage.Serum complement (C) is the principal humoral cytotoxic effector system within the body, and a principal mediator of the biological events of inflammation. Until recently, complement activity was thought to result from the sequential activation of a single series of effector proteins. That is, antigen-antibody complexes were shown to activate in turn the first three components of complement C1, C4, and C2, termed the early components, and activation of these early components led to activation of C3-9, the later components in the complement sequence. A few years ago work from several laboratories established the existence of an alternate pathway of complement activation that bypassed C1, C4, and C2 of the "classical" pathway to enter the complement sequence at the level of C3 (1-4).Previous studies from our laboratory have shown that the alternate pathway is very inefficient at mediating the lysis of both erythrocytes and nucleated cells sensitized with cytotoxic antibody (5). In this report, for the first time, a new cytolytic system is described whereby cells sensitized with cytotoxic antibody can be specifically lysed in the complete absence of intact classical pathway function. Examination of this model has disclosed the existence of a novel cytotoxic complement pathway that is initiated by the attachment of C1 to membrane-bound antibody. The formation of an antigen-antibody-Cl complex (EAC1) leads to activation of components of the bypass or alternate complement pathway, and these in turn activate C3 and the later components of the complement sequence. MATERIALS AND METHODSPreparation of Anti-Forssman Antiserum and Purification of IgG Immunoglobulin. Anti-Forssman antiserum was prepared in a New Zealand white rabbit by repeated intravenous injections of increasing quantities of boiled sheep erythrocyte stromata over a 2.5-week period (10). 2 Weeks after the last intravenous injection of antigen, the rabbit was injected in each footpad with 0.2 ml of an emulsion containing equal volumes of antigen and Freund's complete adjuvant. 2 Weeks later, the animal was bled and the serum was used as a source of IgG hemolytic antibody. The IgG fraction of this antiserum was purified by gel filtration on Sephadex G-200 followed by sucrose density ultracentrifugation as described (6). 0.1 ml of a 1:1280 dilution of this antiserum was sufficient to produce 50% hemolysis of 0.1 ml of ...

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“…In the previously described cases of Clr deficiency, levels of Cls in Clr-deficient patients were also below normal (18,19,31).…”

Section: Discussionmentioning

confidence: 66%

Serum levels of C1q, C1r and C1s in normal and pathologic sera

Bracco

Manni

1974

Arthritis & Rheumatism

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C1q, C1r and C1s protein concentrations were simultaneously assayed in sera of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, autoimmune hemolytic anemia, and viral hemorrhagic fever as well as in healthy adult control subjects. Correlation coefficients between the three subunits of C1 were calculated and the sequential evolution of C1q, C1r, and C1s levels was studied in patients with SLE. In the majority of cases there was a good correlation between C1q, C1r, and C1s; subunit levels increased or decreased in a coordinated fashion. A marked discrepancy between C1q, C1r, and C1s serum concentration was observed in 3 instances. Low C1q coexisted with extremely high C1r and C1s values. It appears that C1r and C1s are closely linked while C1q may vary in a more independent way.

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C1r deficiency: an inborn error associated with cutaneous and renal disease

Cited by 113 publications

References 18 publications

Inherited deficiency of the second component of complement. Rheumatic disease associations.

Inherited deficiency of the second component of complement. Rheumatic disease associations.

A New Complement-Mediated Cytolytic Mechanism—the C1-Bypass Activation Pathway

Serum levels of C1q, C1r and C1s in normal and pathologic sera

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