Vertebral osteomyelitis presenting with bilateral pleural effusions in a leprous patient.

We present a highly rare case of vertebral osteomyelitis due to Salmonella newport that was associated with pleural effusion in a leprous woman. The salmonella infection was considered to be precipitated by her hemolytic anemia resulting from dapsone. The direct spread of infection from the vertebrae led to the pleurisy.

HLA-DQ molecules and the control of Mycobacterium leprae-specific T cell nonresponsiveness in lepromatous leprosy patients.

The major histocompatibility complex (MHC) controls of the outcome of the immune response to T cell-dependent antigens by dictating whether T cell responsiveness will result (MHC-immune response [Ir]genes) or alternatively T cell nonresponsiveness will occur, possibly through the activation of suppressor cells (MHC-immune suppression [Is] genes). In mice, I-A molecules typically restrict antigen-specific helper T cells. In contrast, H-2 I-E molecules have been reported to control nonresponsiveness to a variety of antigens through antigen-specific suppressor cells. In analogy, HLA-DR molecules are the dominant restriction elements for helper T cells in man. This forces the question whether DQ molecules may be involved in controlling nonresponsiveness in man, e.g. through suppression. In one system, T cell nonresponsiveness to Schistosoma japonicum, evidence has been presented supporting this notion. We have now used a second system, Mycobacterium leprae-specific T cell nonresponsiveness, that is typically found in lepromatous leprosy patients. We find positive but limited evidence for a role for HLA-DQ molecules in controlling T cell nonresponsiveness to M. leprae of the 22 nonresponder patients tested, 4 showed a proliferative T cell response to M. leprae after the addition of DQ- but not DR-specific mAb to the cell cultures. In one of the four BCG nonresponders, anti-DQ mAb had a similar effect.

Novel gelatin particle agglutination test for serodiagnosis of leprosy in the field.

We developed a novel gelatin particle agglutination test (MLPA) for the serodiagnosis of leprosy; this test is especially useful for clinical practice and epidemiological surveys of leprosy in countries in which the disease is endemic. The antigen used in the test is the chemically synthesized trisaccharide moiety of Mycobacterium leprae-specific phenolic glycolipid I. MLPA is a simple and easy technique having sensitivity and specificity comparable to those of the conventional indirect enzyme-linked immunosorbent assay. The new technique was found to be useful for monitoring of chemotherapy and predictive diagnosis of high-risk individuals in contact with persons with leprosy and may be useful for the prediction of relapse. We are now preparing to supply a quality-controlled ready-to-use MLPA kit for leprosy control in countries in which leprosy is endemic.

HLA-linked immune suppression in humans.

There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985). However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988). This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive. In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans.