Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients.

OBJECTIVE: To evaluate the frequency of primary immunodeficiencies (PID) in juvenile systemic lupus erythematosus (JSLE) patients. METHODS: Some 72 JSLE patients were analyzed for levels of immunoglobulin classes and IgG subclasses and early components of the classical complement pathway. Determination of C4 gene copy number (GCN) and detection of type I C2 deficiency (D) were also performed. RESULTS: PID was identified in 16 patients (22%): C2D in three, C4D in three, C1qD in two, IgG2D (<20 mg/dl) in four, IgAD (<7 mg/dl) in three, and IgMD (<35 mg/dl) in three; one of these patients presented IgA, C2 and C4D. Two patients had low C4 GCN and two had type I C2D. Demographic data, family history of autoimmune disease and PID, JSLE clinical findings, occurrence of infections, disease activity and therapies were similar in patients with and without PID (p > 0.05). Remarkably, the median of Systemic Lupus International Collaborating Clinics/ACR-damage index (SLICC/ACR-DI) was significantly higher in JSLE patients with PID compared with patients without these abnormalities (p = 0.0033), likewise the high frequency of SLICC/ACR-DI > 1 (p = 0.023). CONCLUSIONS: A high frequency of PID was observed in JSLE patients, suggesting that these defects may contribute to lupus development. Our findings indicate that these two groups of PID should be investigated in severe pediatric lupus.

C2 deficiency in blood donors and lupus patients: prevalence, clinical characteristics and HLA-associations in the Brazilian population.

The objective of the present study was to investigate the prevalence, clinical characteristics, and HLA association of C2 deficiency in the Brazilian population. The frequency of C2 deficiency profile (C2Q degree profile) was 2.2% among 1503 blood donors and 6.6% among 166 patients with systemic lupus erythematosus (SLE). A higher incidence of clinical manifestations possibly related to immune complex disease was observed among blood donors with C2Q degree profile and their relatives with C2Q degree profile when compared to the normal C2 relatives. The comparison of clinical and laboratory features between SLE patients with C2Q degree profile and those with normal C2 revealed earlier disease onset, higher frequency of oral ulcerations and lower frequency of anti-native DNA antibodies in the first group. The HLA study conducted on 18 individuals with C2Q degree profile (11 blood donors and 7 SLE patients) confirmed the previously reported association with the antigens HLA-A25, B18 and DR2, supporting the concept that probably most C2 deficiency cases, throughout the world, are due to a single mutation in the C2 gene in linkage disequilibrium with the A25B18DR2 haplotype.

Major histocompatibility complex genes in a Mexican family with deficiency of the second component of the complement system

La deficiencia hereditaria del segundo componente del complemento es poco frecuente y ha sido reportada principalmente en caucásicos. En México, previamente se ha reportado un caso único con esta alteración. En este trabajo, informamos el caso de un paciente mexicano sin niveles detectables de C2 y ausencia de actividad hemolítica del complemento. El análisis de los marcadores del complejo principal de histocompatibilidad en el caso índice y sus padres mostró los haplotipos HLA-A25, B18, DR2, DQ1, SQ042/HLA-A24, B18, DR2, DQ1, SQ042. La asociación de deficiencia y los antígenos HLA A25, B18 y DR2 está bien documentada en la población caucásica, lo cual sugiere que la deficiencia viene de algún ancestro caucásico en esta familia mexicana

Major histocompatibility complex genes in a Mexican family with deficiency of the second component of the complement system.

Hereditary deficiency of the second component of the complement system is an uncommon condition that has been reported so far mostly in Caucasians. We describe a Mexican patient with undetectable C2 levels and absence of complement hemolytic activity. Major histocompatibility complex (MHC) genes in his family showed that the proband had the MHC haplotypes HLA-A25, B18, DR2, DQ1, SQ042/HLA-A24, B18, DR2, DQ1, SQ042. A strong genetic linkage of the deficiency of the second component of the complement gene and the HLA antigens A25, B18, and DR2, is well established in Caucasian populations. This suggests that the probable origin of the deficiency in our patient was admixture with Caucasian ancestors.

Síndrome vasculítico urticariforme con niveles bajos de complemento hemolítico: presentación de dos casos / Vasculitic urticarial syndrome with low level of hemolytic complement: report of 2 cases

Se presentar dos casos de vasculitis necrotico hemorrágica, con urticaria y niveles séricos bajos de complemento hemolítico. Se trata de un síndrome independiente de lupus eritematoso generalizado. En nuestro medio no se conocen informes similares. La lesión renal al parecer es benigna. Se debe hacer diagnóstico diferencial con púrpura vascular en edad pediátrica

Atypical hypocomplementemic vasculitis syndrome in a child.

We report a patient who developed recurrent urticaria and angioedema at age 2 years, severe hypocomplementemic glomerulonephritis at 11 years, and end-stage renal disease at 14 years. His disease resembled the hypocomplementemic vasculitis syndrome but was atypical in its early age of presentation, severe hypocomplementemia, and progression to end-stage renal disease. Serum C1q levels were extremely low, and C4, C2, C3, and C5 levels were significantly reduced. Serum C1 inhibitor (C1INH) levels were slightly low, presumably from consumption. Circulating C1INH-C1r-C1s complexes were evidenced by reduced ratios of functional to antigenic C1INH and antigenic C1r to C1s. Family members had normal functional and antigenic levels of all complement components studied. The patient's serum, erythrocytes, platelets, and mononuclear cells did not activate complement when mixed with normal target serum. Absence of a circulating complement activator and the low serum C3 and C5 levels suggested the presence of a solid-phase complement activator, possibly related to renal or systemic vascular endothelium. As in patients with homozygous deficiencies of classical pathway components, a severe, prolonged, acquired C1q deficiency may have predisposed this patient to the development of glomerulonephritis.

[The complement system. Normal values and congenital deficiencies in the adult Mexican population]. / El sistema del complemento. Valores normales y deficiencias congénitas en población adulta en México.

Five hundred mexican mestizos, healthy blood donors were evaluated regarding the hemolytic activity of their serum, to assess the function of the complement (C) system. One of them was hypocomplementemic and his serum was unable to promote hemolysis by either classical or alternative pathway. It had normal protein concentrations of C3 and C4, as well as immunoreactive C1, C4, C5, C6, C7 and C8, and lytic factor D. Factor B was not recognizable. It is possible that a genetic deficiency linked to genes codifying for class III products of the major histocompatibility complex is responsible for our findings.