Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy

Abstract

SummaryMycobacterium 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 5 12) or without (n 5 46) reaction (R) at intake and endemic controls (n 5 20). The cohort from Ethiopia included paucibacillary (PB) (n 5 7) and MB (n 5 23) patients without reaction and MB (n 5 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P 0Á01), C4d (P 0Á05) and iC3b (P 0Á05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P 0Á001 without R; P < 0Á05 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 0Á05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions.

Blood coagulation abnormalities in multibacillary leprosy patients

“…These proteins are related but not directly involved in the leprosum clot formation, because high levels of both proteins were also observed in leprosy patients sera weeks prior to leprosum clot occurrence. It was already demonstrated that complement activation products are highly abundant in leprosy reactional episodes, and their presence in the leprosum clot is probably circumstantial [ 41 ]. IHRP, which is also increased in patient’s sera and blood clot, belongs to the inter-alpha-trypsin inhibitor family of acute phase proteins, comprising the common light chain bikunin.…”

Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study

“…Delays in diagnosis of reactions directly translate into negative clinical outcomes, as associated neuropathy not properly diagnosed or treated within the first 6 months of symptoms will likely become permanent 20 alongside the disabilities it may later initiate via recurrent ulcers and other related pathologies 21 . Despite recent scientific progress with respect to complement 22,23 and serum-proteins, particularly CXCL10 (IP-10), as biomarkers associated with onset of reactions 15–17,24–26 , discovery of accurate, clinically useful prognostic biomarkers remains elusive, leaving early diagnosis of reactions a currently unmet need.…”

Host-Related Laboratory Parameters for Leprosy Reactions

“…In addition to APPs, components of the complement system (e.g., C3b, C4b, and iC3b) and immunoglobulins opsonize molecules to promote phagocytosis (114). Notably, terminal complement complex (TCC) and iC3b of the complement system are valuable for the stratification of leprosy patients with or without T1R (115).…”