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Published on: April 8, 2016
In Situ complement activation and T-cell immunity in leprosy spectrum: An immunohistological study on leprosy
Nawal Bahia El Idrissi1, Anand M Iyer2, Valeria Ramaglia1
1Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
Abstract:
Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition worsens often during and long after treatment. Clearance of bacterial antigens including lipoarabinomannan (LAM) during and after treatment in leprosy patients is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves by in situ generation of the membrane attack complex (MAC). Investigating the role of complement activation in skin lesions of leprosy patients might provide insight into the dynamics of in situ immune reactivity and the destructive pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy patients, whether M. leprae antigen LAM deposition correlates with the deposition of complement activation products MAC and C3d on nerves and cells in the surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n = 6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The percentage of C3d, MAC and LAM deposition was significantly higher in the skin biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p = <0.001 and p = <0.001 respectively), with a significant association between LAM and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001 and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary patients, MAC deposition was found on axons and co-localizing with LAM. In skin lesions of paucibacillary patients, we found C3d positive T-cells in and surrounding granulomas, but hardly any MAC deposition. In addition, MAC immunoreactivity was increased in both ENL and RR skin lesions compared to non-reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present findings demonstrate that complement is deposited in skin lesions of leprosy patients, suggesting that inflammation driven by complement activation might contribute to nerve damage in the lesions of these patients. This should be regarded as an important factor in M. leprae nerve damage pathology.
Insights
Mycobacterium leprae lipoarabinomannan (LAM) triggers complement activation, leading to membrane attack complex (MAC) deposition and nerve damage in leprosy patients. This immune response, particularly MAC, is elevated in severe leprosy and reactions, contributing to pathology.
Area of Science:
- Immunology
- Neurology
- Infectious Diseases
Background:
- Leprosy, caused by Mycobacterium leprae, leads to nerve damage that persists post-treatment.
- Bacterial antigens like lipoarabinomannan (LAM) are cleared slowly in leprosy patients.
- Previous work linked M. leprae LAM to peripheral nerve damage via membrane attack complex (MAC) generation.
Purpose of the Study:
- To investigate the role of complement activation in leprosy skin lesions.
- To correlate M. leprae LAM deposition with complement products (MAC, C3d) in skin lesions.
- To understand the dynamics of immune reactivity and pathology in M. leprae infection.
Main Methods:
- Analysis of skin biopsies from paucibacillary, multibacillary leprosy patients, erythema nodosum leprosum (ENL), reversal reaction (RR), and controls.
- Immunohistochemical staining for M. leprae LAM, C3d, and MAC.
- Quantification and statistical analysis of deposition percentages and correlations.
Main Results:
- Significantly higher C3d, MAC, and LAM deposition in multibacillary vs. paucibacillary leprosy.
- Strong association between LAM and C3d/MAC deposition in leprosy skin lesions.
- MAC deposition co-localized with LAM on axons in multibacillary lesions.
- Increased MAC immunoreactivity in ENL and RR lesions compared to non-reactional leprosy.
Conclusions:
- Complement is deposited in leprosy skin lesions, indicating its involvement in pathogenesis.
- Complement activation-driven inflammation likely contributes to nerve damage in leprosy.
- MAC deposition, especially in severe disease and reactions, is a key factor in M. leprae nerve damage pathology.
