Production of a high level of specific IgG4 antibody associated with resistance to albendazole treatment in HLA-DRB1*0901-positive patients with strongyloidiasis.

Abstract

Abstract. Strongyloidiasis, a human intestinal infection with Strongyloides stercoralis, is difficult to treat with drugs. The factors influencing this phenomenon remain unclear. To determine the host factors involved in response to treatment, 46 patients with strongyloidiasis were treated with albendazole, followed-up for 1 year, and separated into two groups: cured and non-cured. Serum levels of specific IgA, IgE, IgG, IgG1, and IgG4 antibodies were estimated using S. stercoralis antigen. Significantly higher titers of IgG4 antibody were observed in the non-cured group than in the cured group (P ϭ 0.016). A total of 88 patients were typed for HLA-DRB1 alleles and analyzed for serum levels of antibody. The S. stercoralis-specific IgG4 antibody titers were significantly higher in the HLA-DRB1*0901-positive group than in the negative group (corrected P ϭ 0.044). These results suggest that HLA-DRB1*0901 is a possible genetic marker for resistance to treatment of S. stercoralis that is associated with elevation of S. stercoralis-specific IgG4 antibody titer.Strongyloidiasis is a human intestinal nematode infection caused by Strongyloides stercoralis. It causes chronic bowel problems, especially in immunocompromised hosts, in which systemic migration of larvae provokes a serious illness due to the unique life cycle of autoinfection of this nematode. 1 It is difficult to completely disrupt this process with drugs against S. stercoralis. 1,2 In Japan, there are many patients with persistent infection in the Southern Islands and Okinawa. 2,3 The factors involved in resistance to treatment remain unknown. Several protocols for treatment have been used, but the efficacy of chemotherapy is not always sufficient to achieve complete treatment. 2,3 In general, there are 2 factors determining the effectiveness of antimicrobial drugs. The first is its pharmacologic effect, including specific cytotoxicity and pharmacokinetics. The other factor is host immunity.The purpose of this study was to determine the factors related to host immunity that influence resistance to treatment of S. stercoralis infection. We examined the HLA-DRB1 gene because its shows the most genetic polymorphism in HLA. Here we show that an increased S. stercoralis-specific IgG4 antibody titer is associated with resistance to treatment, and that patients with HLA-DRB1*0901 produce higher levels of specific IgG4 antibody. MATERIALS AND METHODSStudy population. The efficacy of treatment was evaluated in 46 patients with S. stercoralis infection (29 males and 17 females). The mean ages were 66.4 and 67.1 years, respectively. The frequency of HLA-DRB1 alleles were determined in 88 patients (59 males and 29 females, mean ages ϭ 64.9 and 65.1 years, respectively), including 29 patients who were evaluated for efficacy of treatment. All patients in this study were diagnosed with S. stercoralis infection by an agar plate fecal culture as described 4 at the 1994 annual regional health examination performed in Okinawa prefecture, Japan. Informed consent was obtained fr...

IgG1, IgG4, and IgE antibody responses in human strongyloidiasis by ELISA using Strongyloides ratti saline extract as heterologous antigen

“…Previous studies have demonstrated a predominance of specific IgG4 antibodies to S. stercoralis in chronic infections and an important role of this antibody isotype as modulators in the IgE-mediated immune response (Ishizaka 1982;Atkins et al 1997;Satoh et al 1999). In this context, Genta and Lillibridge (1989) reported that serum factors capable of competing with IgE for S. stercoralis antigens are present on the basophil surface and suggested that such a mechanism could block the IgE-basophil system.…”

“…High levels of specific IgE are usually demonstrated in immunocompetent patients with strongyloidiasis, whereas lower levels are found in the disseminated disease and immunosuppression conditions (Atkins et al 1997;Vercelli et al 1998). Conversely, several reports have indicated that IgG4 antibodies may play a prominent role in chronically infected patients (Genta and Lillibridge 1989;Atkins et al 1999;Satoh et al 1999).…”

Comparative Assessment of the Gelatin Particle Agglutination Test and an Enzyme-Linked Immunosorbent Assay for Diagnosis of Strongyloidiasis

“…This difference in the individual response to infection may affect not only serodiagnosis but also the effectiveness of drug treatment. For example, elevated S. stercoralis-specific IgG4 has been found to be associated with albendazole resistance (26) or ivermectin resistance (16).…”

Association of HLA and post-schistosomal hepatic disorder: A systematic review and meta-analysis

“…The DRB1*0901 allele was also associated with susceptibility to PSHD (OR = 2.14, 95%CI = 1.31-3.48, P = 0.002). The possibility that the HLA-DRB1*0901 allele is primarily responsible for PSHD susceptibility is an interesting point to be considered because IgG4 elevation has been found in individuals with the HLA-DRB1*0901 allele [66] and is positively linked to several systemic fibrosis conditions [67] and schistosomiasis peri-portal fibrosis [68]. It is probable that patients with HLA-DRB1*0901 are prone to produce B cells for specific…”