Pakistan Research Repository

DEFINITION OF THE CHARACTER AND THE ROLE OF IgG SUBCLASSES IN IMMUNOPATHOGENSIS OF ERYTHEMA NODOSUM LEPROSUM (ENL) REACTION IN LEPROSY

Kifayat, Arnawaz (1997) DEFINITION OF THE CHARACTER AND THE ROLE OF IgG SUBCLASSES IN IMMUNOPATHOGENSIS OF ERYTHEMA NODOSUM LEPROSUM (ENL) REACTION IN LEPROSY. PhD thesis, University of Karachi, Karachi.

[img]HTML
16Kb

Abstract

Eythema nodosum leprosum (ENL) is one of the most serious reactional complication in leprosy which can result in permanent disability. ENL occurs towards the lepromatous end (polar lepromatous [LL] and borderline lepromatous [BL] of the disease. The factors which precipitate ENL reactions are still not well understood. Patients undergoing ENL tend to have significantly lower concentration of both IgM and IgG anti-M.leprae antibodies compared to non-reactional (NR) lepromatous patients. However it is unclear if the decrease in antibodies during ENL is related to downregulation of antibody synthesis or due to immune complex formation and deposition in tissues, resulting in decreased concentration in circulation. This issue is addressed in this thesis. Since ENL reactions are occurring in tissues, extravasation of IgG antibodies is more likely to occur than of any isotype. The work is therefore mainly focused on the role of IgG antibody and its subclasses during ENL reactions Polyclonal (PC) and M. leprae specific IgG subclasses (IgG1-4) were quantitated by enzyme linked immunosorbent assays (ELISA) in 150 leprosy patients (LL or BL) and 108 endemic controls (EC). All four IgG subclass antibodies showed a significant elevation (p<0.0001) of PC IgG subclasses in NR-LL/BL patient group compared to EC group. When NR-LL/BL were compared with patients undergoing ENL reaction, a selective decrease of PC IgG1 (p<0.005), PC IgG2 (p<0.0001) and PC IgG3 (p<0.001) antibodies were observed in the group undergoing ENL reaction. PC IgG4 antibodies were not significantly different M. leprae antigen specific IgG subclass antibodies in leprosy patients were also detected in all IgG subclasses but a pre-dominant response was observed in IgG1 (̃300 fold) and IgG3 (-110) antibodies in NR-LL/BL patient compared to EC group. In patients undergoing ENL reactions there was a selective decrease in M. leprae specific IgG1 (p<0.05) and IgG3 (p<0.001) antibodies compared to NR-LL/BL patient group. This observation was further supported by immunoblotting analysis comparing NR-LL/BL and ENL patients serum pools. Both analysis confirmed selective decrease in M. leprae specific IgG1 and Igg3 during ENL reactions To see if this selective decrease in antibody during ENL reaction is a result of down regulation of antibody synthesis the frequency of antibody secreting B-cells (ABSCs) in the blood compartment was determined by ELISPOT assays and related to serum immunoglobulin concentrations (μg/ABSC) in LL/BL patients with and without ENL reaction. Since B-cell are activated in the tissue compartments, a decrease in antibody synthesis should result in a decrease in the ratio of serum antibody concentration/ABSC. Paired samples (n=13) were analysed during acute ENL reaction and after the reaction had subsided to identify changes associated with ENL reaction. IgG1 showed higher antibody concentration ratio (μg/ABSC) in patient groups. The mean concentration ratio of IgG3 and IgG4 was similar in acute-ENL and post-ENL goups. Igg2 showed the reverse trend and were lower during ENL and increased in Post-ENL group. These results strongly support the conclusion that there is an increase in polyclonal (PC) IgG1 synthesis during ENL reactions. Since the increase is transient in nature, upregulation of IgG1 is associataed with ENL Thus, decrease in M. leprae specific IgG1 observed during ENL is not related to down regulation of B-cell responses.Decrease in circulating IgG1 and IgG3 antibodies is therefore most likely a result of antibody deposition in tissue compartments such as the skin. An intriguing observation was the inverse relationship of IgG1 and IgG2 antibodies which indicates a hobeostatic balance and may be related to cross regulation of these two isotypes In conclusion, leprosy patients undergoing ENL reaction have a dysregulation of selective IgG isotypes viz: IgG1 and IgG3. During ENL reaction there is an up regulation of IgG1 synthesis probably due to activation of B-cells in the tissue compartments by factors yet to be identified. The sudden increase in synthesis of antibodies may result in increased concentration of antibodies at the local disease site with high concentration of bacterial load which may result in immune complex formation and deposition. Since IgG1 antibodies are highly efficient in fixing complement, such deposition may be the root cause of ENL symptomatology. Our future studies would concentrate on identifying factors which differentiate IgG1 synthesizing B-cells

Item Type:Thesis (PhD)
Uncontrolled Keywords:erythema nodosum leprosum, leprosy, igm, igg, immunosorbent assays
Subjects:Biological & Medical Sciences (c) > Biological Sciences(c1) > Microbiology(c1.8)
ID Code:1303
Deposited By:Mr. Muhammad Asif
Deposited On:27 Jan 2007
Last Modified:04 Oct 2007 21:05

Repository Staff Only: item control page