Hla-unked genetic control of host response to mycobacterium lepræ

In an attempt to confirm an HLA-linked effect on the course of Mycobacterium leprae infection observed in families from Surinam (South America), we conducted a similar family study in an endemic area in India. We observed a significant (P less than .05) excess of identical HLA-GLO haplotypes only from healthy parents among siblings affected with tuberculoid leprosy. Compared with healthy controls, unrelated patients with tuberculoid leprosy (n = 15) showed a significant heterogeneity at the HLA-DR locus (P less than .05). This heterogeneity was caused by an increased frequency of HLA-DRw2 (.93 versus .53, P less than .05), particularly of DRw2 homozygotes (.53 versus .11, P less than .005), and a decreased frequency of HLA-DRw6 (.07 versus .58, P less than .005). We observed a significant (P = .03) preferential segregation of DRw2 from DRw2 heterozygous parents not affected with tuberculoid leprosy to children with the tuberculoid type of the disease. These data confirm an HLA-linked control of susceptibility to tuberculoid leprosy only, and suggest a recessive inheritance of this trait for which HLA-Drw2 appears to be a genetic marker.

HLA-linked Control of Susceptibility to Tuberculoid Leprosy and Association with HLA–DR types*

HLA-DR-associated genetic control of the type of leprosy in a population from surinam.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease presents a wide spectrum of clinical manifestations, ranging from lepromatous to tuberculoid leprosy; each form may be punctuated by episodes of acute exacerbation, called reactional states. These polar forms and reactional states appear to be determined by immunologic interactions between the host and the microorganism. This review describes the different measurable parameters that permit the classification of a particular form according to clinical, bacteriologic, histologic, and immunologic spectra. Secondly, the current state of knowledge on essential immunologic features of leprosy is presented, with a description of the various alterations of cellular and humoral immune responses that can be tested by specific and nonspecific methods. The last part of the review is devoted to an analysis of the leprosy spectrum and to speculations about a number of possible factors that may influence the immune response of the host in a manner analogous to that observed in experimental models.

The Immunology of Leprosy: Speculations on the Leprosy Spectrum

This review examines the evidence for involvement of MHC-associated factors in host immune response to Mycobacterium leprae, by collating HLA studies of sporadic and familial leprosy and discussing possible HLA-related immunological mechanisms in determining host response. Formal linkage analysis of 109 multiple-case families with data available for HLA haplotype segregation showed that under a three-allele recessive model for susceptibility to leprosy, linkage was observed between the HLA complex and a leprosy susceptibility locus at a recombination fraction of 20%. The significance of the linkage relationship was confined to families with at least two tuberculoid leprosy offspring and neither parent affected. When one parent was affected, with leprosy of any clinical type, lod scores could neither implicate nor exclude linkage between HLA and leprosy susceptibility and this apparent paradox can be explained by the presence of an additional, non-HLA linked susceptibility locus for leprosy.

ItaliaM. Andrade

Papers

Hl-a antigens in leprosy