C4, BF, C3 Allele Distribution and Complement Activity in Healthy Aged People and Centenarians

Diego Bellavia, Giovanni Frada, Pietro Di Franco, Salvatore Feo, Claudio Franceschi, Paolo Sansoni, and Melchiorre Brai

Department of Immunology, Institute of Internal Medicine, and Department of Cellular and Developmental Biology, University of Palermo, Palermo, Italy.

The aim of this study was to examine the complement system and the distribution of some human leukocyte antigen (HLA) class III alleles (C4, BF) in healthy aged people (77 centenarians and 89 elderly subjects). We have also studied the alleles of C3, a complement component genetically unrelated to HLA, the immunochemical levels of C4 and C3 and serum functional hemolytic activity for classical (CH50) and alternative (AP50) complement pathways. The levels of C3 and C4 and the CH50 and AP50 were found to be within the normal range. The frequencies of C3, BF, and C4A alleles were similar in the cohorts that have been studied. For C4B null allele (C4BQO), a trend toward an increase in the older cohort was observed, although the differences were not significant after statistical correction. Our data suggest that the complement system is well-preserved in centenarians and elderly subjects and class III HLA antigens are equally distributed in aged cohorts.

Characterized by the absence of the phenotypic product (QO; quantity 0), BF is also polymorphic with less allotypes (12). In a previous study, the frequency distribution of class III alleles was investigated in Hungarian old people, and a lower frequency of C4AQO and C4BQO was observed suggesting that the presence of null alleles, especially C4BQO, can negatively influence life expectation (13,14). We could not confirm these data in a previous study in which we examined 82 Sicilian elderly persons (average age 80 years) and 304 controls (15). To better understand the influence of C4 and BF allomorphisms on the expectation of life, we studied the C4 and BF alleles in 77 centenarians and in 89 elderly subjects from Italy. We also analyzed the C3 alleles in these long-lived individuals to investigate the polymorphism of a complement component unrelated to HLA.

There are several studies that address the changing equilibrium of the immune system aging both in experimental animals and humans (1,2). Individuals usually exhibit changes of both T- and B-segments with a high proportion of aged individuals showing hypergammaglobulinemia and increased signs of autoimmunity (3-5), although usually without any of the associated pathologies. Innate immunity has also been studied in and generally there are no age-related changes if they are selected according to the criteria for health status (6). Several parameters of nonspecific immunity have been studied in long-lived people, but practically no information is available on their complement system. In this study, we examined the immunochemical levels of C4 and C3 and serum functional hemolytic activity of the classical (CH50) and the alternative (AP50) complement pathways to ascertain if changes of this segment of nonspecific immunity occur in the elderly.

Methods

The study groups included 77 healthy centenarians (13 males and 64 females, mean age 101.4 years, range 100 to 107 years), 89 elderly subjects (20 males and 69 females, mean age 72 range 70 to 89 years), and 235 young subjects less than 50 years old (134 males and 101 females, mean age 35 years, range 18 to 49 years). The elderly subjects were selected for being healthy according to the Senieur protocol (16). Centenarians were in good mental and physical condition. They were free of tumors or immunological disorders; most of them also fulfilled the criteria of the Senieur protocol. All the individuals under study were Italian and unrelated, and all of them gave their informed consent. The serum samples were fresh or stored at -80C until tested.