ABSTRACT
As the central component of the complement system, C3 has sensory and effector functions bridging innate and adaptive immunity. It is plausible that common genetic variation at C3 determines either serum C3 level or susceptibility to systemic lupus erythematosus (SLE), but only a single, Japanese, study has currently showed genetic association. In a cohort of 1371 individuals from 393 UK white European SLE families, we quantified serum C3 and genotyped C3 tagSNPs. Using a Bayesian variance components model, we estimated 39.6% serum C3 heritability. Genotype/serum C3 association was determined by mixed linear models. Single nucleotide polymorphism (SNP) rs344555, located in a haplotype block incorporating the 3' end of C3, was associated with serum C3 (P=0.007), with weaker associations observed for other SNPs in this block. In an extended cohort of 585 SLE families the association between C3 variants and SLE was assessed by transmission disequilibrium test. SNP rs3745568 was associated with SLE (P=0.0046), but not with serum C3. Our disease associated SNP differs from that highlighted in the Japanese study; however, we replicate their finding that genetic variants at the 3' end of C3 are associated with serum C3. Larger studies and further fine mapping will be required to definitively identify functional variants.
Subject(s)
Complement C3/genetics , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Polymorphism, Single Nucleotide , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Middle Aged , United Kingdom , White People/geneticsABSTRACT
To study the diagnostic significance of antifilarial IgG subclasses in the clinical spectrum of brugian filariasis, IgG1, IgG3 and IgG4 antifilarial antibodies were determined in an exposed population comprising 74 asymptomatic amicrofilaraemics, 30 microfilaraemics, 20 lymphangitis and 16 elephantiasis patients resident in Narathiwart province, an area endemic for Brugia malayi lymphatic filariasis in southern Thailand. The dominant isotype of antifilarial antibody was IgG4. A significantly higher percentage of individuals were positive for IgG1 in the microfilaraemic and lymphangitis groups compared with the elephantiasis and endemic normal patients, while a significantly higher positive rate of IgG3 was found in those with lymphangitis. The possible role of these isotypes for diagnostic purposes and the pattern of antibody response in various clinically manifesting groups are discussed.
Subject(s)
Antibodies, Helminth/analysis , Brugia malayi/immunology , Filariasis/diagnosis , Immunoglobulin Isotypes/analysis , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Animals , Antibodies, Helminth/blood , Antibody Specificity , Case-Control Studies , Child , Elephantiasis/diagnosis , Elephantiasis, Filarial/diagnosis , Endemic Diseases , Enzyme-Linked Immunosorbent Assay/methods , Feces/chemistry , Female , Filariasis/immunology , Humans , Immunoglobulin Isotypes/blood , Male , Middle Aged , Sensitivity and Specificity , ThailandABSTRACT
OBJECTIVES: To determine clinical manifestations, prognostic factors, and therapeutic outcomes of severe pneumococcal infection. METHODS: Hospitalized patients with specimens cultured positive for Streptococcus pneumoniae were identified retrospectively by reviewing hospital records from 1992 to May 1998 at Siriraj Hospital. RESULTS: Of 205 evaluable cases, 130 (63.4%) patients were male. Nineteen (9.3%) patients were less than 2 years old, 29 (14.1%) were between 2 and 13 years, 99 (48.3%) were between 14 and 60 years, and 58 (28.3%) were over 60 years of age. From 1992 to 1997, the average admission rate was highest (36.4%) between January and March (range = 20-45%). Average admission rates during other periods ranged from 20.0% to 23.1%. Pneumonia (50.7%) and acute exacerbation of chronic obstructive pulmonary disease or infected bronchiectasis or bronchopneumonia (21.0%) were the most frequent diagnoses, followed by meningitis (14.6%) and primary sepsis without localized lesion (8. 3%). The mortality rate during the first 7 days of hospitalization was 28.8%, and thereafter, 11.7%. The odds ratios (95% CI) of old age, congestive heart failure, and alcoholism for death were 3.4 (1. 4-8.2), 8.6 (0.97-76.1), and 8.0 (3.1-20.9), respectively. For pneumonitis only, mortality rates among alcoholic and nonalcoholic patients were 76.9% and 39.6%, respectively (P = 0.025). CONCLUSIONS: Patients who were alcoholic, over 60 years of age, or had congestive heart failure were vulnerable to severe pneumococcal infection with significant mortality, in spite of proper selection of empirical antimicrobials. Diabetes mellitus and multiple myeloma also contributed to late mortality after 7 days of hospitalization.
