A transient rise in agalactosyl IgG correlating with free interleukin 2 receptors, during episodes of erythema nodosum leprosum.

The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine and not galactose (%GO) has previously been shown to be raised in rheumatoid arthritis (RA), Crohn's disease (CD) and tuberculosis (Tb), but to be normal in sarcoidosis (SA), and in both lepromatous and tuberculoid leprosy. However we have now studied %GO in sequential serum samples collected from lepromatous leprosy patients undergoing episodes of erythema nodosum leprosum (ENL). During ENL %GO is transiently raised, and this rise parallels an increase in circulating interleukin 2 receptors (IL-2R). These findings confirm that changes in T cell function occur during ENL. Moreover it appears that %GO rises when there is, simultaneously, T-cell-mediated tissue damage and an acute phase response (RA, CD, Tb, ENL), but not when there is an acute phase response without major T cell involvement, or chronic T cell activity alone (SA, and tuberculoid leprosy). We suggest therefore that %GO is an indicator of a type of T cell activity with broad immunopathological implications.

The role of cytokines in the immunopathology of tuberculosis, and the regulation of agalactosyl IgG.

Tuberculosis is characterised by necrosis in the lesions and in skin-test sites, and by fever and weight loss. In contrast, other diseases with chronic T cell mediated responses, such as uncomplicated leprosy and sarcoidosis, have non-necrotising lesions with little systemic upset. Crude sonicates of M. tuberculosis and M. leprae prepare skin sites for TNF-mediated damage via a pathway which unexpectedly appears to involve CD8+ T cells, and both mycobacteria contain potent triggers of TNF release (lipoarabinomannan and peptidoglycan derivatives). These observations can partially explain the pathology of tuberculosis, but fail to explain why similar events do not normally occur in leprosy. It now seems likely that the answer lies in the existence of novel regulatory pathways. A recently recognised correlate (or consequence) of diseases characterised by T cell-dependent tissue-damaging pathology and cytokine release, is an increase in the level of agalactosyl IgG. This behaves like a T cell-dependent acute phase reactant, and is raised in tuberculosis, rheumatoid arthritis, and Crohn's disease, but not in sarcoidosis or uncomplicated leprosy. Thus it may act as a marker for a type of pathology of very broad significance, though its functional role remains obscure.

Absence from sera from normal individuals or from rifampin-treated leprosy patients (THELEP trials) of antibody to rifamycin-protein or rifamycin-membrane conjugates.

It has been reported that normal individuals have precipitating antibody which binds to rifamycin-conjugated proteins. An enzyme-linked immunosorbent assay has failed to confirm this claim, although antibodies demonstrable in a solid-phase binding assay are easily raised in mice if complete adjuvant is used. Moreover, no antibodies to rifamycin-protein conjugates were found in sera from the patients included in THELEP trials of six rifampin-containing regimens. Similarly, there was no antibody by the indirect Coombs test performed in another laboratory. Further studies using rifamycin-membrane conjugates regarded as more likely to be immunogenic in vivo also failed to reveal antibody in patients' sera, although this technique revealed an interesting antibody in one of four control sera known to be positive by the indirect Coombs test.

Behandlung eines subakut-kutanen Lupus erythematodes mit Thalidomid / Treatment of subacute cutaneous lupus erythematosus with thalidomide

A patient with subacute-cutaneous lupus erythematosus showed no response to corticosteroids and azathioprine. Treatment with thalidomide resulted in a dramatic clearing of skin lesions but failed to improve pathological laboratory tests.

Antibodies against Mycobacterium leprae antigen 7 from birth to 18 months of age: an indicator of intra-uterine infection in leprosy.

All babies of three non-leprosy mothers and ten tuberculoid leprosy mothers and four of five babies of mothers with inactive lepromatous leprosy showed a decline in serum concentration of antibodies against M. leprae antigen 7 during the first 4 months of life, as expected from catabolism of maternal IgG. By contrast, ten of twenty babies of mothers with active lepromatous leprosy showed a decline in concentration of anti-M. leprae 7 antibodies considerably less than expected. This indicates that these babies have been stimulated by M. leprae antigen 7, either as free antigen or by viable M. leprae before birth, and thus that leprosy may occur as a congenital infection. Studies of anti-M. leprae antibodies in repeated serum samples obtained during the first 18 months of life indicated that children of mothers with bacilliferous leprosy are frequently exposed to M. leprae to a sufficient extent to stimulate the immune system of the baby to production of anti-M. leprae antibodies during this period. The consequences of this exposure to M. leprae should be ascertained by careful clinical studies.