1.
Persistent Anti-Borrelia IgM Antibodies without Lyme Borreliosis in the Clinical and Immunological Context.
Markowicz, M, Reiter, M, Gamper, J, Stanek, G, Stockinger, H
Microbiology spectrum. 2021;9(3):e0102021
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Borrelia burgdorferi (BD) specific Immunoglobulin (Ig) antibodies are a diagnostic key for infection and Lyme’s disease. Generally, IgM is reflective of recent infection and converts to IgG after several weeks during disease progression or inadequate treatment. Yet, in the early phase of infection, not all cases present with antibodies and at the same time, both IgM and IgG can persist in healthy people after tick exposure or treatment. This study sought to investigate further the common phenomenon of persistence of IgM, regardless of symptomatic BD infection. The study examined the serum of 59 predominantly female patients, that showed persistent IgM antibodies in the absence of IgG. The majority of subjects experienced non-specific symptoms, and half of them had a history of antibiotic treatment, yet IgM persisted. The observation went on for >6 months, thus excluding the likelihood of any acute infection. The results showed that in people with lower IgM count a greater improvement of non-specific symptoms was observed as opposed to those with higher IgM count. Furthermore, the assay identified multiple cross-reactivity patterns from other plants, bacteria and human tissue to the antigen-binding receptor OspC typically used for BD testing. The authors postulate that the phenomena of IgM persistence potentially originates from a previous infection with BD, but may be maintained in some individuals by continuous stimulation with cross-reactive antigens from other sources. This is important knowledge for the interpretation and improvement of testing for BD. Of clinical interest here is that IgM persistence, beyond the acute phase, maybe no longer be reflective of the original BD infection. And in such cases, non-specific symptoms may be sustained by other triggers such as foods, other microorganisms and autoimmunity.
Abstract
The aim of the study was to investigate the etiology of persistent IgM antibodies against Borrelia burgdorferi sensu lato (sl) and to analyze their association with nonspecific symptoms. The study group comprised individuals with persistent IgM antibodies in the absence of IgG. The relation between ELISA values and time elapsed since past erythema migrans (EM) was analyzed. Previous antibiotic treatments were assessed. The association between persistent IgM and nonspecific symptoms was evaluated statistically. Specificity of IgM antibodies for outer surface protein C (OspC) of B. burgdorferi sl was examined by immunoblotting. Further, we investigated the cross-reactivity with Borrelia-unrelated proteins. Fifty-nine patients (46 women; 78%) were included in the study group. The mean IgM-ELISA values did not change significantly during follow-up (median 6.2 months). The mean ELISA value in the study group was dependent on time elapsed since past EM. Nonspecific symptoms improved significantly more often in patients with lower IgM ELISA results. Persistent IgM antibodies were specific for the C-terminal PKKP motif of OspC. Cross-reacting C-terminal PKKP antigens from both human and prokaryotic origins were identified. We demonstrate that the C-terminal PKKP motif plays a main role for the reactivity of persistent Borrelia IgM toward OspC. However, cross-reactivity to other eukaryotic and/or prokaryotic antigens may hamper the specificity of OspC in the serological diagnosis of Lyme borreliosis. Lack of improvement of nonspecific symptoms was associated with higher IgM ELISA values. IMPORTANCE The reactivity of human IgM with the outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is frequently used to detect Borrelia specific IgM in commercial immunoassays, and such antibodies usually occur in the early phase of the infection. We identified a group of individuals with persistent Borrelia IgM without symptoms of Lyme borreliosis. We used their sera to demonstrate that the C-terminal epitope of OspC binds the IgM. Strikingly, we found that the same epitope occurs also in certain proteins of human and environmental origin; the latter include other bacteria and food plants. Our experimental data show that these Borrelia-unrelated proteins cross-react with the OpsC-specific IgM. This knowledge is important for the development of serologic assays for Lyme borreliosis and provides a cross-reactive explanation for the persistence of Borrelia-IgM.
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Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease.
Wang, HY, Li, Y, Li, JJ, Jiao, CH, Zhao, XJ, Li, XT, Lu, MJ, Mao, XQ, Zhang, HJ
World journal of clinical cases. 2019;7(16):2189-2203
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Crohn's disease and ulcerative colitis are relapsing gut inflammatory diseases that are usually referred to as Inflammatory Bowel Disease (IBD). It may be triggered by an imbalance in immune response in response to environmental factors such as diet. The aim of this retrospective study was to evaluate the presence of IgG and IgE mediated antibodies to food antigens in IBD patients. There were one hundred and thirty-seven IBD patients participating in this study, including forty Ulcerative colitis patients and ninety-seven Crohn's disease patients against fifty healthy controls to test serum IgG antibodies to fourteen specific food antigens and serum IgE antibodies to fourteen specific food antigens. There were significantly higher IgG antibodies in response to food antigens in Crohn's disease patients than in Ulcerative colitis patients and healthy controls. Food antigens such as tomato, corn, egg, rice, and soybean exhibited varying levels of IgG antibody responses in Crohn's disease patients and ulcerative colitis patients. Smokers were more likely to develop IgG reactions. Further robust research is needed to examine more IgG-specific food antigens to help manage IBD with an elimination rotation diet. The results of this study can help healthcare professionals understand the importance of diagnosing food intolerances when treating IBD.
Abstract
BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear. AIM: To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD. METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn's disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression. RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831). CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.