HLA-A, -B, -C and -DR antigen profile in pulmonary tuberculosis in North India.

Investigations for the HLA-A, -B, -C and -DR antigens were conducted on 124 random North Indian patients with confirmed diagnosis of pulmonary tuberculosis by the demonstration of acid fast bacilli in the sputum. 109 appropriately matched controls from the same ethnic background were also tissue typed. No significant deviation was observed in the HLA-A, -B, and -C locus antigens. With the HLA-DR typing, there was a marginal increase in DR2 and a concurrent significant decrease in DRw6 in the patient group. These deviations were, however, insignificant when correction for the P value was made. ABO blood group typing results indicate that blood group 'O' may afford protection against TB. The involvement of both DR2 and DRw6 is interesting as it is also implicated in leprosy, another mycobacterial disease. The results suggest the possibility of a common gene in the MHC for both tuberculosis and leprosy.

Ultrastructure of skin in erythema nodosum leprosum.

The ultrastructural changes observed in erythema nodosum leprosum lesions were gross damage to blood vessels, particularly the endothelial cells, and deposition of immune complexes in vessel walls. Infiltrating cells and alteration of the ground substance formed a constant feature of the reaction. These changes are characteristic of an immune complex reaction.

Vascular changes in nerves in experimental leprosy--an ultrastructural study.

Ultrastructural observations made on the blood vessels of nerves in CBA/J mice with experimentally produced M. leprae infection revealed cytoplasmic filamentous structures along with large sized vacuoles in the endothelial cells and reduplication of peripericytal basement membranes in the 6-9 months of infection. In animals with late infection of 9-15 months duration, the endothelial cells presented foamy appearance caused by an increase in the number of vacuoles. These findings are suggestive of degenerative changes in the endothelial cells probably due to circulation of noxious substance in the blood stream.

Mast cell and Mycobacterium leprae in experimental leprosy.

The association of mast cells and lepra bacilli was studied in the foot pad skin of immunosuppressed mice inoculated with 10(5) lepra bacilli. The mice were killed at intervals varying from 2 1/2-14 months postinoculation. M. leprae are found in large numbers in nerves, blood vessels, muscle fibres, hair follicles, sweat and sebaceous glands. Mastocytosis and extensive degranulation are seen at similar sites. Since these are the structures most affected in leprosy where the lepra bacilli and degranulating mast cells accumulate, there appears a close relationship between the two. This could be due to the composite role of mast cells in host tissue response and mastocytosis and degranulation may be related to this.

Nerve damage in leprosy-a teased fibre study of sciatic nerves in experimental mice.

The extent of nerve damage was assessed in the sciatic nerves of CBA/J mice with experimental leprosy by the teased single fibre preparations. Morphological changes in the fibres were observed upto 15 months of infection and compared with control animals of the same age groups. During 4 to 9 months period, the fibres showed paranodal enlargements, widening of the Schmidt-Lantermann incisures, paranodal and whole segmental demyelination. In addition, fragmentation of axons with the formation of myelin ovoids in the schwann tubes was also observed in animals with 9 to 15 months of infection. While segmental demyelination was predominant early in infection, axonal degeneration was more evident in advanced infection. These findings may possibly, explain the underlying mechanism of nerve damage in human leprosy.

Mast cell and Mycobacterium leprae in experimental leprosy.

A asociacao de mastocitos e bacilos de Hansen foi estudada na pele do coxim plantar de camundongos timectomizados e submetidos a 900r de radiacao total inoculados com 10 elevado a 5 M. leprae. Os camundongos foram mortos em intervalos que variaram de 2 e meio a 14 meses apos a inoculacao. Bacilos foram encontrados em grande quantidade nos nervos, vasos sanguineos, fibras musculares, foliculos pilosos, glandulas sudoriparas e sebaceas.Mastocitose e granulacao extensa foram observadas nesses sitios. Ja que estas estruturas sao as mais afetadas na hanseniase, nas quais os bacilos e os mastocitos granulosos se acumulam, parece haver uma estreita correlacao entre os dois. Isto pode ser devido ao desempenho multiplo dos mastocitos na resposta dos tecidos hospedeiros; a mastocitose e a granulacao podem estar relacionadas com esses fatos

HLA and sporadic tuberculoid leprosy: a population study in Maharashtra, India.

A population study to test whether associations between HLA and sporadic--i.e. non-familial--tuberculoid leprosy exist was undertaken in a hyperendemic area in India. Since previous family studies in the same area had shown both non-random haplotype segregation in the family members affected with tuberculoid leprosy and the preferential segregation of HLA-DR2 into tuberculoid leprosy patients, an increased frequency of DR2 among the "sporadic" patients was expected. However, no heterogeneity for HLA was detected between patients and controls. These findings could indicate that tuberculoid leprosy is a heterogeneous disease with regard to genetic background.

Natural suppressor cells in human leprosy: the role of HLA-D-identical peripheral lymphocytes and macrophages in the in vitro modulation of lymphoproliferative responses.

Six families with HLA-D-identical siblings suffering from leprosy were studied. Lymphocytes and macrophages isolated from the peripheral blood were co-cultured with allogeneic, HLA-D-identical cells and stimulated with M. leprae antigens and concanavalin A. Tuberculoid patients had circulating lymphocytes which showed marked functional suppression of lymphoproliferative responses to antigen and mitogen. In contrast, lepromatous patients showed weak lymphocyte suppressor activity. Macrophages derived from responder individuals augmented, while those derived from lepromatous patients inhibited, M. leprae-induced proliferation of lymphocytes.

Natural supressor cells in human leprosy: the role of HDLA-D-identical peipheral lymphocytes and macrophages in the in vitro modulation of lymphoproliferative responses

Six families with HLA-D-identical siblings suffering from leprosy were studied. Lymphocytes and macrophages isolated from the peripheral blood were co-cultured with allogeneic, HLA-D-identical cells and stimulated with M. Leprae antigens and concanavalin A. tuberculoid patients had circulating lymphocytes which showed marked functional suppression of lymphoproliferative responses to antigen and mitogen. In contrast, lepromatous patients showed weak lymphocyte suppressor activity. Macrophages derived from responder individuals augmented, while those derived from lepromatous patients inhibited, M. leprae-induced proliferation of lymphocytes.

HLA-linked control of susceptibility to tuberculoid leprosy and association with HLA-DR types.

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 segregation of tuberculoid leprosy: confirmation of the DR2 marker.

Families with multiple cases of leprosy were tested for HLA (histocompatibility leukocyte antigen)-linked control of susceptibility to tuberculoid leprosy and association with HLA-DR2. Thirty-one non-HLA genetic markers were also examined for indications of non-HLA-linked genetic factors that might control susceptibility to tuberculoid leprosy. A significant (P = 0.002) preferential inheritance of HLA-DR2 by siblings affected with tuberculoid leprosy, but not by healthy siblings nor by siblings affected with lepromatous leprosy, was observed. In addition, combined family data showed a significant (P less than 0.0025) excess of identical HLA haplotypes inherited from healthy parents by siblings affected with tuberculoid leprosy. Segregation on non-HLA polymorphisms did not deviate significantly from what would have occured randomly. These data are compatible with a recessive inheritance of HLA-linked susceptibility to tuberculoid leprosy. The preferential segregation of DR2 observed in children with tuberculoid leprosy (P less than 0.001 for the combined data from India) indicates that the HLA-linked susceptibility gene is either DR2 or in linkage disequilibrium with it.

Ultrastructure of nerve in erythema nodosum leprosum (ENL).

Gross changes of myelinated fibres and Schwann cells at different degenerative stages were present in all five ENL nerve lesions. Besides these changes, infiltrating cells mainly macrophages, deposition of excessive collagen and perineurial vessel damage were also observed.

In vivo response of mast cells to lepromatous serum.

Adult healthly mice of pure line Institute strain were given, into the foot pad, an intradermal injection of normal human serum in group A and lepromatous serum in group B. In both groups, the animals were killed at varying time intervals. Serial paraffin sections of the foot pad skin 5--7 mu thick, were cut and stained with haematoxylin and eosin, toludine blue, acridine orange and para-bromaniline. On comparing the two groups, in group B the response of mast cells was more prompt, pronounced and persistant. The increase in the number of cells was accompanied by explosive degranulation around nerves, blood vessels and muscles. This response became less by 15 days but did not disappear completely. There were still few intact cells in the dermis. Histamine, heparin and 5-Ht showed a corresponding rise. The importance of the findings is discussed.