Complement factors in newly diagnosed Nigerian schizoprenic patients and those on antipsychotic therapy.

The role of Complement factors in the pathogenesis of psychiatric disorders is enormous, but the data on levels and functions of complement factors in patients with schizophrenia are scanty and conflicting. To address this issue, levels of Complement regulators (C1 inhibitor and C3 activator) and complement factors (C1q, C3c, C4 and C5) were determined in the serum of newly diagnosed drug free schizophrenic patients, schizophrenic patients on medication and healthy subjects using immune-plates. C1q was significantly reduced in newly diagnosed schizophrenic patients or schizophrenic patients on medication compared with the controls. C3c was significantly reduced in newly diagnosed schizophrenic patients compared with controls or schizophrenic patients on medication. The levels of C3 activators, C1 inhibitors and C4 were similar in the two groups of schizophrenic patients compared with the controls. It may be concluded from this study that C1q is deficient in schizophrenic patients; and that C3c may differentiate newly diagnosed schizophrenia from schizophrenic patients on medication.

Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Aß by microglia.

Complement components and their receptors are found within and around amyloid ß (Aß) cerebral plaques in Alzheimer's disease (AD). Microglia defend against pathogens through phagocytosis via complement component C3 and/or engagement of C3 cleavage product iC3b with complement receptor type 3 (CR3, Mac-1). Here, we provide direct evidence that C3 and Mac-1 mediate, in part, phagocytosis and clearance of fibrillar amyloid-ß (fAß) by murine microglia in vitro and in vivo. Microglia took up not only synthetic fAß(42) but also amyloid cores from patients with AD, transporting them to lysosomes in vitro. Fibrillar Aß(42) uptake was significantly attenuated by the deficiency or knockdown of C3 or Mac-1 and scavenger receptor class A ligands. In addition, C3 or Mac-1 knockdown combined with a scavenger receptor ligand, fucoidan, further attenuated fibrillar Aß(42) uptake by N9 microglia. Fluorescent fibrillar Aß(42) microinjected cortically was significantly higher in C3 and Mac-1 knockout mice compared with wild-type mice 5 days after surgery, indicating reduced clearance in vivo. Together, these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAß by microglia, providing support for a potential beneficial role for microglia and the complement system in AD pathogenesis. © 2012 Wiley Periodicals, Inc.

Hypocomplementemic urticarial vasculitis in mixed connective tissue disease.

Urticarial vasculitis is characterized clinically by urticaria-like skin lesions and histologically by leukocytoclastic vasculitis. It may be idiopathic or associated with various conditions such as infections, hematologic disorders, drugs, and connective tissue diseases, primarily systemic lupus erythematosus; an association with mixed connective tissue disease (MCTD) has rarely been reported. We present a case of hypocomplementemic urticarial vasculitis in a patient with MCTD that responded to hydroxychloroquine after a period of corticosteroid dependence.

Disfunción aguda del hemisferio cerebral derecho e hipocomplementemía / Acute dysfunction of right hemisphere and hypocomplementemia

La alteración aguda de las funciones cerebrales superiores del hemisferio derecho suelen pasar inadvertidas o ser inadecuadamente interpretadas en pacientes en edad pediátrica. Se presenta una niña de 9 años, zurda, sana, que durante las dos semanas previas a la consulta padeció episodios de parestesias, una convulsión clónica del miembro superior izquierdo y cambios progresivos en su conducta con irritabilidad, llanto o risa inmotivados, coprolalia, copopraxia e insomnio. Al examen se hallaba temerosa, agresiva, verborrágica. Refería "verse hinchada como un globo", "los objetos se agrandaban o se movían rápidamente" y veía "príncipes y brujas de pelo verde y ojos color púrpura". Utilizaba exclusivamente el miembro superior derecho sin detectarse anormalidades del sistema motor, sensitivo o en la coordinación. Podía leer y realizar cálculos matemáticos, pero no escribir, dibujar ni realizar construcciones con cubos. E.E.G.: ondas lentas en hemisferio derecho; L.C.R.: 9 linfocitos, resto s/p; TC y RNM normal. Serología para virus negativa. F.A.N., anti-ADN, prot. Creativa, células L.E., test del látex [-]. C3: 65 mg por ciento [V.N.: 150 ñ 30 mg por ciento]; C.I.C.: 33 por ciento [V.N.: 14 ñ 5 por ciento]. Además del tratamiento con oxcarbacepina, se adicionaron esteroides, con lo cual mejoró la sintomatología. Al año de seguimiento se hallaba asintomática y los exámenes inmunológicos eran normales. Conclusión: El compromiso predominante de la región parietooccipital derecha explicaría la sintomatología referida. Una vasculitis hipocomplementémica sería la probable etiología

Hereditary complement factor I deficiency.

We describe four cases (from three families) of hereditary factor I deficiency, bringing the total number of cases now reported to 23. In one family there are two affected siblings: one has suffered recurrent pyogenic infections; the other is asymptomatic. In the second family, the patient had recurrent pyogenic infections and a self-limiting vasculitic illness; in the third family, the patient suffered recurrent pyogenic and neisserial infections. All four patients had markedly reduced concentrations of C3 in the serum (family 1 propositus: 28%; family 1 asymptomatic sibling: 15%; family 2: 31%; and family 3: 31% normal human serum) which was in the form of C3b. Low IgG2 levels may occur in primary C3 deficiency, and a reduction in IgG2 concentration to 1.14 g/l (normal: 1.30-5.90 g/l) was found in the patient from family 2. Using radioligand binding assays, we demonstrated increased binding of C3b to erythrocytes in a patient with factor I deficiency. This C3b could not be cleaved by autologous serum but could be cleaved by normal serum or purified factor I. We review and compare the published cases of C3, factor H and factor I deficiency.