Persistent Clq deficiency in a patient with a systemic lupus erythematosus-like syndrome.
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Circulating immune complexes have been detected in 100% of 59 patients with dermatitis herpetiformis (D.H.), and in 100% of 27 patients with coeliac disease (C.D.). Three methods for detecting immune complexes were employed: radiobioassay, which gave an incidence of 77% in D.H. and 81% in C.D.; C1q binding activity, with which the incidence was 83% and 96%, respectively; and precipitation with 4% polyethylene glycol (69% positivity in D.H., 100% in C.D.). The immune complexes in D.H. and C.D. were compared with those in sera from 23 patients with systemic lupus erythematosus (S.L.E.). Multiple complexes of differing properties were found in D.H. and C.D. but not in S.L.E. The varying nature of the complexes in D.H. and C.D. may account for the damage to different tissues (skin, small intestine, reticuloendothelial system). Low third component of complement was found in 49% and low C4 in 20% of D.H. patients. C3 hypocomplementaemia was found in 26% of patients with C.D.
Immune complexes have been found in several chronic diseases of unknown aetiology and identification of the constituents of the complexes might lead to recognition of aetiological agents. Sera and renal tissues from patients with amyotrophic lateral sclerosis (A.L.S.) were studied for evidence of immune complexes. C1q precipitation testing demonstrated that sera from 10 of 25 patients with classic A.L.S. bound significantly more radiolabelled C1q than sera from 15 controls. In renal glomeruli studied for deposition of host 1gG, C3, fibrinogen, and albumin by means of direct immunofluorescence, 9 of 33 patients with A.L.S. (27 biopsy and 6 necropsy specimens) had moderate amounts of both IgG and C3 of granular basement membrane and mesangia. This pattern of immunofluorescence is characteristic of immune complex deposits. Of these 9, 8 had rapidly progressive neurological courses, whereas among the remaining 18 patients with no evidence of immune-complex disease, 9 of 12 available for clinical follow-up had stable or slowly progressive courses.
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Eight patients with systemic lupus erythematosus (S.L.E.) have been treated with plasmapheresis. In four patients in whom immunochemical studies indicated high levels of circulating immune complexes, the removal of 5-8 litres of plasma weekly produced a striking clinical and immunochemical improvement. The four other patients, with only minor complement disturbances and no direct evidence of circulating immune complexes, could not be shown to benefit from plasmapheresis and one patient in this group died of cerebral lupus despite intensive treatment with cytotoxic drugs. It is concluded that plasmapheresis may be of value as an adjuvant to the treatment of acute S.L.E.
The P component of amyloid (protein AP, pentagonal unit) has been isolated from normal serum by using its hitherto undescribed calcium-dependent affinity for agarose. The presence of P component in all forms of amyloid may be due to this calcium-dependent binding to certain polyanions.
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Large immune complexes are present in the circulation of patients with primary biliary cirrhosis and result in the activation of complement by the classical pathway. Such large complexes are capable of producing tissue damage. The granulomatous lesions surrounding the small bile-ducts within the liver of patients with primary biliary cirrhosis and the vasculitis, rheumatoid arthritis, and associated lesions are all compatible with immune complex injury. It is postulated that such large complexes could be formed in the vicinity of the bile-ducts by an antigen absorbed from the bile or biliary epithelium. Complexes reaching the systemic circulation might be responsible for the associated extra-hepatic diseases.
Forty patients attending the Prince Henry Hospital migraine clinic have been investigated for evidence of complement activation related to migraine. These patients had a history of clinically similar migraine attacks. Levels of serum complement components were determined in nine patients, both in and out of migraine. Comparison of these levels showed significant reductions in C4 and C5 during headache. In a further 31 patients C3 breakdown products were sought when these patients were headache-free. They were detected in the plasma of three patients who proceeded to a migraine attack but not in the plasma of the remaining twenty-eight who did not. These findings suggest the presence of complement activation, which could explain many of the previously reported phenomena associated with migraine.
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