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D M Scollard

Publications and source records attributed to D M Scollard.

At least 37 records · Page 2Linked to original sources
PubMed1993

Time and change: new dimensions in the immunopathologic spectrum of leprosy.

Accumulating evidence of diversity within leprosy types suggests that the traditional application of the concept of an immunopathologic spectrum has been too narrow; new dimensions are necessary to accommodate these observations. The spectrum is a continuous one, not a series of steps, and heterogeneity within each type may be based on factors both inherited ("causal") and acquired ("consequences"). Current clinical and epidemiological data indicate that time is an important variable in several respects. Long increments of time must be considered; major shifts in immune responsiveness from one end of the spectrum to the other may occur in individual patients over many years. The age of onset and duration of illness may generate different risks of immuno-inflammatory reactions in leprosy, also after many years. New methods must therefore be devised to evaluate the immunologic status of patients over several years. The powerful tools of molecular biology and immunology are likely to be more fruitful if applied with new questions in mind to help us understand the diversity within the spectrum and the differing potential for changes in immunologic response over a long period of time.

Erythema Nodosum↗
PubMed1992

Immune complexes and antibody levels in blisters over human leprosy skin lesions with or without erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is a serious complication of lepromatous leprosy, affecting skin and peripheral nerves in a large percentage of these patients, and is presumed to result from spontaneous immunologic changes. Its pathogenesis is poorly understood, although histopathologic features have suggested immune complex (IC)-mediated injury. Abundant circulating antibody is present but no convincing correlation has been established between circulating IC and ENL. We have examined cutaneous leprosy lesions in vivo using blisters induced by prolonged gentle suction to determine whether or not IC are demonstrable in lesions with or without ENL, using an IC assay based on monoclonal rheumatoid factor binding. We also examined whether antibodies involved in such IC are produced locally or reach the skin via the circulation. Surprisingly large quantities of IC were found in ENL lesions, and in some cases the quantities were significantly higher than in matching serum. Total IgG, IgA, and IgM in the skin were not higher than expected, however. Attempts to demonstrate increases in intracutaneous levels of specific anti-Mycobacterium leprae antibodies were unsuccessful. This is the first report of the demonstration of IC in suction blister fluid. The results indicate that large quantities of IC may be present in cutaneous leprosy lesions and are consistent with the hypothesis that they are formed in situ when circulating antibody combines with antigen in the skin. The nature of the antigen in these IC remains undefined.

Antibodies↗
PubMed1991

Studies of human leprosy lesions in situ using suction-induced blisters: cell changes with IgM antibody to PGL-1 and interleukin-2 receptor in clinical subgroups of erythema nodosum leprosum.

To examine the immunopathogenesis of type 2 erythema nodosum leprosum (ENL) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 57 patients with reactions (19 acute ENL and 38 chronic ENL), 61 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells, IgM antibody to PGL-1 and Tac peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During ENL reactions: a) the lesions in chronic ENL showed a decreased number of CD8+ (T-suppressor) cells and increased helper/suppressor ratio as compared to those in acute ENL and non-reactional leprosy; b) Tac peptide and IgM antibody to PGL-1 levels were elevated in the chronic ENL lesions; c) and systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population and IgM antibody to PGL-1 but did not change CD8+ cell population and the levels of Tac peptide in the lesions. The elevated levels of Tac peptide were localized in the skin lesions while increased levels of IgM anti-PGL-1 seemed to be filtered from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of decreased CD8+ and relatively increased CD4+ cells, are important features of chronic, recurrent ENL reactions and may be an intermittent or cyclic phenomenon during the reaction. Understanding the mechanisms of these spontaneous changes in immunity in leprosy will enlarge our knowledge of reactions and of the underlying determinants of delayed type hypersensitivity and cell-mediated immunity in leprosy, which in turn will allow us to realize the potential for artificially manipulating these responses as proposed with vaccines or immunotherapy.

Adolescent↗
PubMed1991

Inside the skin: the local immune and inflammatory milieu in leprosy.

Skin lesions of leprosy have become a rich source of new information about the mechanisms involved in the uniquely broad spectrum of human responsiveness to M. leprae. Recent technological advances in immunology and molecular biology have been applied to the study of skin lesions using 3 approaches: immunohistologic studies of skin biopsies from leprosy lesions, correlated assessment of cell subsets and soluble immunologic mediators, and studies of the effects of the inoculation of exogenous lymphokines into the lesions. Results from these studies suggest that an immunologic equilibrium may exist among long-established lesions across the spectrum so that, although T-helper and -suppressor cells are present in different proportions, immunologic activity is at a low, similar level in all types of lesions. Exogenous lymphokines can alter this equilibrium and temporarily change the histologic picture. Spontaneous immunologic changes occurring in acute leprosy reactions may also lead to changes in T cell subsets and quantities of lymphokines.

Erythema Nodosum↗
PubMed1990

Studies of human leprosy lesions in situ using suction-induced blisters. 2. Cell changes and soluble interleukin 2 receptor (Tac peptide) in reversal reactions.

To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 10 patients with reactions, 24 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells and Tac-peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During reversal reactions: a) the lesions contained an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide levels were elevated in half of the lesions; c) the increases in Tac peptide and CD4+ cells were directly correlated; and d) systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population. These findings were localized to the skin, and do not represent simple filtration of these components from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an important feature of reversal reactions, and may be an intermittent or cyclic phenomenon during the reaction. Findings in active patients without reactions are consistent with the hypothesis that differing states of immunologic equilibrium have been established in different portions of the leprosy spectrum. In reversal reactions we may, therefore, be examining immunologic processes set in motion when a pre-existing equilibrium has been upset by spontaneous, natural events. The mechanism of such spontaneous changes in immunity in leprosy is of considerable interest, not only to understand the reaction, but also to examine the underlying determinants of delayed-type hypersensitivity and cell-mediated immunity in leprosy and the potential for artificially manipulating these responses, as proposed with vaccines or immunotherapy.

Adult↗
PubMed1990

Cell changes and soluble interleukin-2 receptors (Tac peptide) in leprosy reversal reactions using suction-induced blisters.

The cellular contents and soluble interleukin-2 receptor (IL-2R) [Tac peptide] of skin blisters induced by suction over 7 reversal reaction (RR) patients were examined using immunoperoxidase and ELISA techniques respectively. The helper T activity (CD4+ cells) and helper:suppressor ratio were significantly greater in borderline lepromatous (BL) lesions with RR than in quiescent BL lesions. Interestingly, the intracutaneous levels of Tac peptide were elevated and directly correlated with the increases in CD4+ cells. The systemic administration of corticosteroids revealed a reduction in the numbers of CD4+ cells in the lesions. These results indicate that RRs are manifestations of a spontaneous increase in delayed type hypersensitivity (DTH) and possibly cell mediated immunity (CMI) in leprosy patients. The mechanism of such changes in immunity is of considerable value in understanding reversal reactions and the underlying determinants of DTH and CMI in leprosy and this in turn will have a bearing on the potential for proposed vaccines or immunotherapy.

Adult↗
PubMed1989

Studies of human leprosy lesions in situ using suction-induced blisters. 1. Cellular components of new, uncomplicated lesions.

The cellular contents of blisters induced by suction over new, uncomplicated leprosy lesions, and in the skin of cured, control patients, have been examined with enzyme- and immuno-histochemical staining over a period of 4 days. The total cellularity of the blisters varied over a wide range, not correlated with the type of leprosy. Mononuclear cells predominated at all times studied, with nearly equal percentages of monocytes and T lymphocytes. The T-helper: suppressor ratio was significantly greater in BT than in BL and LL lesions at 48 hr. Suction blisters offer a painless, quantitative, reproducible, multiple-sampling method for obtaining cells from the cutaneous infiltrates of leprosy for phenotyping or functional analysis.

Blister↗
PubMed1989

Hepatitis B antigen and antibody in patients with leprosy: a study of three resettlement villages in Thailand.

It remains uncertain whether the cellular immune abnormalities of patients with lepromatous leprosy interfere with resolution of hepatitis B virus (HBV) infections. To investigate this question in an area coendemic for the two diseases, we determined the prevalence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in: 1) 204 leprosy patients living in three leprosy resettlement villages; 2) 198 contacts living in the same villages; and 3) 44 newly diagnosed leprosy patients in Thailand. Within the villages, the prevalence of HBsAg positivity was inversely related to age, tended to be more frequent in patients with tuberculoid than lepromatous leprosy, and was similar after age adjustment among persons with and without leprosy. The prevalence of HBV markers found in newly diagnosed patients was similar to that in the villagers. We conclude that extensive HBV transmission had occurred in the resettlement villages and that the natural history of HBV infection was similar in persons with, whether tuberculoid or lepromatous, and without leprosy.

Adolescent↗
PubMed1988

Release of soluble interleukin-2 receptors (Tac peptide) in vivo during human immune responses to tuberculin.

Cutaneous levels of soluble interleukin-2 receptor (Tac peptide) have been measured in tuberculin responses in 13 human volunteers by assaying the fluid present in suction-induced blisters at various times after injection of standard purified protein derivative of tuberculin (PPD). Low levels of Tac peptide were found in blisters without prior injection of PPD and in PPD-negative individuals, and maximal levels of Tac peptide were correlated with increased induration at 48 hr (r = 0.69, P = 0.04) in PPD-positive subjects. This is the first report of measurement of Tac peptide in vivo in a defined immune response in man, and may offer a new approach to the study of human immune function in vivo.

Adult↗
PubMed1988

Illness beliefs of leprosy patients: use of medical anthropology in clinical practice.

Illness beliefs of 61 patients identified as having leprosy were assessed by Kleinman's Explanatory Model Format. Our patients used a wide variety of etiologic theories which were grouped in categories such as venereal disease, heredity, dangerous food, sin, karma, and humoral disorders. Despite efforts at patient education, very few patients adopted the concept of bacterial infection to explain their illness. The patients identified their illness with a variety of different labels, some of which had associations with particular symptoms. Leprosy was perceived and experienced more as a series of acute disorders not necessarily related to one another. The various theories of illness were instrumental in directing treatment choices which included a number of indigenous healing practices. Such information may be useful in improving patient care and compliance by providing practitioners with interpretive strategies for communicating with their patients.

Adolescent↗
PubMed1987

Skin blister immunocytology. A new method to quantify cellular kinetics in vivo.

A method is described using tuberculin purified protein derivative (PPD) as a model to follow the in vivo cellular immune response. This combines induction of a local response, formation of skin blisters, and staining of the cells appearing in the sterile exudate over time, using standard cytopreparatory and immunoperoxidase techniques. Skin blisters were induced over sites previously injected intradermally with PPD or control saline using suction over a template on the forearm. The cells which appeared in the exudate at 24, 36, 48 and 72 h were collected on small cellulose filters which were divided into several parts. The cells on the filter segments were then stained using a biotin-avidin immunoperoxidase method with a panel of monoclonal antibodies, and with enzyme histochemical techniques. This allowed quantitative estimation over an extended period of total numbers of each cell type responding as a local expression of cellular immunity. The kinetics of an early, non-specific inflammatory response could be distinguished from the later immune response using total cell counts. Maximal cell counts correlated well with PPD induced induration at 48 h, showing an overwhelming predominance of mononuclear cells. Over 72 h, the number of non-specific esterase (NSE) positive cells (macrophage) declined while Leu4 positive cells (T cells) increased. OKT4 positive cells (T helper) outnumbered OKT8 positive cells (T suppressor) as the response developed. This method enables the direct quantitative assessment of cell populations arriving at the site of an immune response using a simple inexpensive technique which is painless, non-invasive and non-scarring.

Adult↗
PubMed1987

Cellular and humoral immune response to a phenolic glycolipid antigen (PhenGL-I) in patients with leprosy.

The ability of phenolic glycolipid I (PhenGL-I) of Mycobacterium leprae to stimulate in vitro lymphocyte proliferation (LP) was tested in cultures of peripheral blood cells from 42 patients with leprosy in Chicago and Thailand, 9 individuals with household contact in Thailand, and 10 unexposed North American controls. Only 10 responders (24%) were found among the patients, and the degree of LP was small. Responders were found among patients with lepromatous (18%) or tuberculoid (30%) leprosy without relation to age, complications, duration of treatment, or lepromin responsiveness. The specificity of the response was supported by a lack of response to two other glycolipids, by responses by T cells but not B cells, and by the observation that three of four responders tested maintained their responses to PhenGL-I for at least 1 year. Serum immunoglobulin M (IgM) and IgG antibodies were measured in the same patients by using PhenGL-I or its terminal monosaccharide conjugated to a bovine serum albumin carrier in an enzyme-linked immunosorbent assay. The presence of IgM antibody correlated negatively with LP to lepromin and to PhenGL-I in patients with tuberculoid leprosy. We conclude that circulating T cells from some leprosy patients proliferate in the presence of PhenGL-I in vitro, but the response is weak, possibly due to concomitant suppression or inhibition. The predominance of IgM antibody to PhenGL-I may be related to a lack of a T-helper-cell-mediated switch to IgG antibody response.

Antibodies, Bacterial↗
PubMed1986

Lymphocyte transformation in lepromatous leprosy: a study of the influence of disease activity and symptom duration.

The lymphocyte hyporesponsiveness to M. leprae of patients with active lepromatous leprosy has been well described. This immune defect is less well understood in terms of its time of origin, possible reversibility and specificity. To further examine the persistence and specificity of this abnormality, lymphocyte transformation tests of 93 leprosy patients to lepromin, BCG and PHA were studied. Among lepromatous patients, a decreased response to M. leprae was seen, whether the disease was active or inactive. Decreased responses to BCG were found in lepromatous patients with active disease, but not in those with inactive disease. The duration of patient symptoms was not associated with differences in LTT responses among the active lepromatous patients.

Adolescent↗
PubMed1985

A study of the immunological effects of cimetidine in patients with lepromatous leprosy.

To test the capacity of cimetidine to enhance cellular immunity in patients with lepromatous leprosy (LL), cimetidine was given for one month to 29 inactive LL patients and 3 active LL patients. Immune function was monitored with skin tests (lepromin, PPD, candida, and trichopytin), lymphocyte transformation tests (phytohemagglutinin, BCG, and Dharmendra lepromin), and quantitation of peripheral blood lymphocyte subpopulations. A small but significant "booster" response to PPD was the only change observed in the study of patients with inactive disease, and leprosy-related reactions did not occur. In the few active LL patients studied, neither immune enhancement nor leprosy-related reactions were observed. The results of this investigation suggest that cimetidine can be used safely in patients with inactive lepromatous leprosy.

Adjuvants, Immunologic↗
PubMed1981

Glomerulonephritis in leprosy.

A renal biopsy from a patient with lepromatous leprosy but no history of erythrema nodosum leprosum (ENL) showed histologic, immunofluorescent, and ultrastructural features typical of immune-complex glomerulonephritis. A literature review found reports of 187 renal biopsies from leprosy patients, with glomerulonephritis in 31% of the cases, and a variety of other renal lesions. This accumulated evidence demonstrates that, contrary to widely held opinion, there is no association between glomerulonephritis and a history of ENL. Furthermore, it suggests that glomerulonephritis in leprosy patients has a similar incidence in lepromatous and non-lepromatous cases. These observations have an important bearing on concepts regarding the pathogenesis of immune complex glomerulonephritis in leprosy and the humoral immune mechanisms in patients with leprosy.

Antigen-Antibody Complex↗