Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy
N. Bahia El Idrissi
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Search for more papers by this authorS. Hakobyan
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
Search for more papers by this authorV. Ramaglia
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Search for more papers by this authorA. Geluk
Department of Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands
Search for more papers by this authorB. Paul Morgan
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
Search for more papers by this authorP. Kumar Das
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Department of Clinical Immunology, Colleges of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
Search for more papers by this authorCorresponding Author
F. Baas
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Correspondence: Frank Baas, Department of Genome analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands. E-mail: [email protected]Search for more papers by this authorN. Bahia El Idrissi
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Search for more papers by this authorS. Hakobyan
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
Search for more papers by this authorV. Ramaglia
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Search for more papers by this authorA. Geluk
Department of Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands
Search for more papers by this authorB. Paul Morgan
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
Search for more papers by this authorP. Kumar Das
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Department of Clinical Immunology, Colleges of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
Search for more papers by this authorCorresponding Author
F. Baas
Department of Genome Analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands
Correspondence: Frank Baas, Department of Genome analysis, Academic Medical Center, Amsterdam, 1105 AZ, the Netherlands. E-mail: [email protected]Search for more papers by this authorSummary
Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi-bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci-bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (P ≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions.
Supporting Information
Additional Supporting information may be found in the online version of this article at the publisher's web-site:
| Filename | Description |
|---|---|
| cei12767-sup-0001-suppfig1.tif32.6 MB |
Fig. S1. Terminal complement complex (TCC) serum levels of leprosy patients followed at reaction and after treatment. TCC serum levels of leprosy patients at reaction do not change after treatment, indicating that treatment does not affect complement activity in leprosy. |
| cei12767-sup-0002-suppfig2.tif18.9 MB |
Fig. S2. Complement activation in pauci-bacillary (PB) and multi-bacillary (MB) leprosy patients from Ethiopia. Meso Scale discovery (MSD) platform for measuring complement activation products C4d (a), mid-borderline (Bb) (b), inactive complement activation fragment (iC3b) (c) and terminal complement complex (TCC) (d) in serum from PB (n = 7) and MB (n = 23) leprosy patients, showing a significant increase in MB compared to PB leprosy patients for C4d [mean PB = 7·99 mg/l, standard error (s.e.) = 1·99 versus mean MB = 27·15 mg/l, s.e. = 4·04; P = 0·04], Bb (mean PB = 24·91 mg/l, s.e. = 2·39 versus mean MB = 28·62 mg/l, s.e. = 1·99; P = 0.03), iC3b (mean PB = 13·15 mg/l, s.e. = 1·94 versus mean MB = 22·39 mg/l, s.e. = 1·92; P = 0·02) and TCC (mean PB = 2·02 mg/l, s.e. = 0·23 versus MB = 4·03 mg/l, s.e. = 0·28; P = 0.003). The error bars represent the standard error of the mean. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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