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IgG Antibodies & IBD/IBS - NED Infobite
BANT's scientific NED InfoBites are designed to provide key elements of the latest research using plain language. They provide quick overviews on particular health issues and nutrition topics for a speedy introduction to the science. Visually attractive and easily shareable with clients and social media followers.
2024
Abstract
Elimination diets based on IgG-dependent food sensitivity are showing promise for conditions such as IBS, Crohn's disease and migraines. This NED Infobite highlights a number of clinical trials where IgG food sensitivity testing is put to the test.
Sponsored Journal Article
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Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
Gut Microbes is an open access journal which publishes research on intestinal microbiota, gastrointestinal, liver and cardiac disease, cancer, and irritable and inflammatory bowel conditions. The intestinal microbiota plays a pivotal role in human physiology. Characterizing its structure and function has implications for health and disease, impacting nutrition and obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and others. Gut Microbes provides a platform for presenting and discussing cutting-edge research on all aspects of microorganisms populating the intestine.
2022
Abstract
Covid-19 is a disease of the lungs, which differentially affects those it infects. There are currently no therapies that have been approved for use in Covid-19 patients. However recent evidence has highlighted a possible link between the gut and the lungs, known as the gut-lung axis indicating a new avenue for investigation. Previous trials on probiotics have indicated a role in infections such as cold and flu highlighting a possible role in Covid-19 infection. This randomised control trial of 300 Covid-19 patients aimed to determine the efficacy and safety of a probiotic known as AB21 containing several strains of Lactoplantibacillus plantarum and Pediococcus acidilactici. The results showed that after 30 days, the rate of remission from Covid-19 was higher in those who were given the probiotic, which was regardless of age, sex, confounding metabolic illness, viral load, and days from symptom start. Symptom duration and viral load were also reduced with probiotic use. Higher amounts of Covid-19 associated immune activity and lower biomarkers of inflammation were also reported following probiotic use. Probiotic use was shown to be safe during Covid-19 infection. It was concluded that the use of AB21 in Covid-19 patients was safe and associated with increased viral and symptom resolution compared to placebo, possibly driven by immune alterations via the gut-lung axis. This study could be used by healthcare professionals to seriously consider the use of this probiotic to stimulate immune activity and aid viral and symptom resolution in patients suffering from Covid-19.
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Decreasing Migraine Frequency with Nutrition
As the pioneer and global leader of Functional Medicine, the Institute of Functional Medicine (IFM) leads and catalyses the efforts of a large and expanding Functional Medicine ecosystem, including providers, educators, payers, industry leaders, regulators, and influencers.
2022
Abstract
It is proposed that nutritional interventions for migraines might reduce migraine occurrence and increase the quality of life for migraine sufferers. Immune mediated food sensitivities have been implicated as an underlying factor and evidence suggests that IgG based elimination diets may reduce the quantity of migraines. Supplements such as CoQ10, magnesium citrate, riboflavin, cinnamon, and vitamin D (if deficient) may also reduce the frequency of migraine attacks. Given that cardiovascular and neurological comorbidities have been closely associated with migraines it is interesting that dietary approaches such as the DASH (Dietary Approaches to Stop Hypertension) and MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diets have been shown to reduce headache severity. The role of fatty acids is also highlighted as studies have linked omega-3 fatty acid intake with migraine prophylaxis, providing another avenue for migraine support.
Sponsored Journal Article
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IgG-Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome
Headache publishes original articles on all aspects of head and face pain including communications on clinical and basic research, diagnosis and management, epidemiology, genetics, and pathophysiology of primary and secondary headaches, cranial neuralgias, and pains referred to the head and face. Monthly issues feature case reports, short communications, review articles, letters to the editor, and news items regarding AHS plus medicolegal and socioeconomic aspects of head pain. This is the official journal of the American Headache Society.
2022
Abstract
OBJECTIVES To evaluate therapeutic potential of the immunoglobulin G (IgG)-based elimination diet among migraine patients with irritable bowel syndrome (IBS). BACKGROUND Food elimination has been suggested as an effective and inexpensive therapeutic strategy in patients with migraine and concomitant IBS in the past studies. METHODS A total of 21 patients (mean [standard deviation] age: 38.0 [11.2] years; 85.7% females) diagnosed with migraine and IBS were included in this double-blind, randomized, controlled, cross-over clinical trial composed of baseline (usual diet), first diet (elimination or provocation diets), and second diet (interchange of elimination or provocations diets) phases and 4 visits. RESULTS IgG antibody tests against 270 food antigens revealed mean (standard deviation) reaction count to be 23.1 (14.1). Compared with baseline levels, elimination diet per se was associated with significant reductions in attack count (4.8 [2.1] vs 2.7 [2.0]; P < .001), maximum attack duration (2.6 [0.6] vs. 1.4 [1.1] days; P < .001), mean attack duration (1.8 [0.5] vs. 1.1 [0.8] days; P < .01), maximum attack severity (visual analog scale 8.5 [1.4] vs. visual analog scale 6.6 [3.3]; P < .001), and number of attacks with acute medication (4.0 [1.5] vs. 1.9 [1.8]; P < .001). There was a significant reduction in pain-bloating severity (1.8 [1.3] vs. 3.2 [0.8]; P < .05), pain-bloating within the last 10 days (3.2 [2.8] vs. 5.5 [3.1]; P < .05), and improvement obtained in quality of life (3.6 [1.4] vs. 2.9 [1.0]; P < .05) by the elimination diet as compared with provocation diet. CONCLUSION Our findings indicate that food elimination based on IgG antibodies in migraine patients who suffer from concomitant IBS may effectively reduce symptoms from both disorders with possible positive impact on the quality of life of the patients as well as potential savings to the health-care system.
Sponsored Journal Article
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The Clinical Use of IgG Food Sensitivity Testing with Migraine Headache Patients: a Literature Review
Current Pain and Headache Reports provides in-depth review articles contributed by international experts on the most significant developments in the field. By presenting clear, insightful, balanced reviews that emphasize recently published papers of major importance, the journal elucidates current and emerging approaches to the diagnosis, treatment, management, and prevention of pain and headache.
2022
Abstract
Purpose of Review: This literature review describes the relationship between IgG food sensitivities and their relation to migraine headaches. Recent Findings: IgG food sensitivities have been linked to various symptoms and disorders. While food sensitivities and intolerances are recognized within the clinical medicine community, diagnosing these sensitivities and intolerances can be challenging because symptoms are usually delayed hours to days and may not occur after every exposure to the allergen. Some reports indicate that foods such as chocolate, cheese, cow’s milk, eggs, and red wine may be triggers for migraine headaches. Summary: The pathophysiology of migraine headaches is not well understood. Some evidence supports the use of IgG food sensitivity testing to determine food sensitivities and intolerances. IgG food sensitivity testing may prove to be a beneficial tool for healthcare practitioners, especially for patients experiencing migraine headache symptoms. Utilizing IgG food sensitivity testing to create customisable dietary recommendations for patients may allow healthcare providers to treat migraine headaches without the use of medications.
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Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study.
Ostrowska, L, Wasiluk, D, Lieners, CFJ, Gałęcka, M, Bartnicka, A, Tveiten, D
Journal of clinical medicine. 2021;10(19)
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IBS, also known as irritable bowel syndrome, is a debilitating condition characterised by abdominal pain, irregular bowel movements, and changes in the consistency of stool. Symptoms of IBS may appear shortly after eating a meal. Excluding foods high in FODMAP carbohydrates, such as fermentable oligo- and di-saccharides, mono- and disaccharides, and polyols, or following an elimination rotation diet to reduce IgG-dependent food hypersensitivity, which has been shown to improve IBS symptoms previously. The purpose of this open-label study is to investigate the effectiveness of a low-FODMAPS diet and an elimination rotation diet based on IgG as well as a control diet in reducing symptoms of IBS. During the eight-week study, 73 female subjects with a mix of IBS were assigned to either of the three dietary treatments. Compared to the other diet groups, the IgG based elimination rotation diet group showed a significant improvement in the IBS symptoms and comorbid symptoms after the intervention period. In order to determine whether IgG-mediated food hypersensitivity plays a role in IBS and the efficacy of an IgG-dependent elimination rotation diet in the general population, further robust research is required. Healthcare professionals, however, can make use of these results to gain a better understanding of how an IgG based elimination diet tailored to each individual can improve IBS symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- After implementing the three diets, among patients with IBS-M, a statistically significant reduction of the frequency of the idiopathic abdominal pain, abdominal pain after a meal, abdominal pain during defecation, and sensation of incomplete defecation before and after the diet plans, were only found in Group 2.
- Significantly, only in the Group 2 IgG based elimination-rotation-diet was there a high decrease or complete disappearance of dyspeptic IBS symptoms and co-morbidities together with IBS symptoms.
- This study shows that a personalised dietary approach is more effective in treating IBS than generalised diet recommendations, with elimination diets focused on IgG antibodies providing the best results.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Science supports the use of a low-FODMAP diet for symptom relief of IBS. However, more recently evidence suggests that IBS is a low-grade inflammatory disease that may result from or lead to IgG-dependent food hyper-sensitivities.
This study compared the effectiveness of three dietary treatment plans in 73 female patients diagnosed with mixed-form IBS based on Rome III criteria and no other gastrointestinal condition over 8 weeks.
The 3 dietary groups were:
- Group 1-low FODMAP diet
- Group 2- IgG based elimination-rotation-diet
- Group 3-control diet (control group)
Diets of G1 and G2 were determined individually by a dietitian, based on low-FODMAP dietary information and results from IgG food sensitivity testing respectively. Group 3 received nutrition advice from a gastroenterologist.
In G1, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). Gurgling sensation and gastric fullness also reach statistical significance in G1.
IBS symptoms as well as co-morbid symptoms significantly improved or disappeared completely in G2 (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008; sensation of incomplete defecation p = 0.001; difficulty to defecate (constipation) p = 0.002; bloating p = < 0.001; gurgling sensation < 0.001; gastric fullness p = < 0.001. However, blood and mucus in the stool were impossible to test because the symptoms were not reported by any patient during the 2nd examination). (p-values less than 0.05 were considered statistically significant).
In group G3 no statistically significant improvements were seen in any measure.
Based on the results of this open-label study, it was concluded that personalised dietary interventions were more effective in the treatment of IBS-M patients than generalised diet recommendations. Dietary elimination based on IgG food sensitivity test results had the greatest impact on IBS and related symptoms.This study supports results from other studies showing an IgG-guided diet as an effective strategy in co-morbid conditions such as fatigue, headache/migraine, and skin conditions.
Conflicts of Interest
C.F.J.L., M.G. and A.B. are employees of the Institute of Microecology in Poznan ,where the ImuPro tests were determined. D.T. is the Head of Laboratory and shareholder of Lab1, offering ImuPro tests in Norway.
Clinical practice applications:
- Low FODMAP diets studies (NICE) showed GI improvements for abdominal pain, abdominal cramps, diarrhoea, gas, and bloating, largely because FODMAPs mainly cause an excessive production of gas, leading to discomfort and pain and an increased osmotic effect leading to increased bowel movement and diarrhoea. However 30% of patients still suffered from bloating on the FODMAP diet. Gurgling sensation decreased from 65% to 15%, and gastric fullness decreased from 58% to 11% in the patients on the low FODMAP diet.
- A potential new approach to resolve functional symptoms of gastrointestinal conditions could be to start with an IgG-guided elimination diet, as it was proven to be the more effective diet in this open study, and in cases of persistent symptoms, it could be combined with a low-FODMAP diet.
- Calprotectin is currently one of the best-known diagnostic markers indicating mucosa inflammation and changes in the inflammation intensity. In this study serious intestinal inflammation was diagnosed at the faecal calprotectin concentration of >50 mg/kg of stool. During the first examination, no statistically significant differences were found in calprotectin concentrations between the compared groups of patients, and the values were low, suggesting that the included patients suffered from low-grade inflammation and were suitable for diet alteration as the best choice of treatment.
Limitations:
- The main limitations of this study are the open-labeled nature, the low number of participants and the bias of only including female participants with only the patients in the G2 group tested for IgG food antibodies.
- Foods consumed by the patients before they entered the study were not ascertained.
Considerations for future research:
- Claims that IgG food antibodies only reveal exposure to food and not intolerance should be reinvestigated in larger double-blinded studies.
Abstract
Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.
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Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review.
Chen, M, Qin, R, Jiang, M, Yang, Z, Wen, W, Li, J
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;104:415-422
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The rapidly spreading nature of COVID-19 has put an emphasis on the importance of fast diagnosis. Gold standard diagnosis is through reverse transcription polymerase chain reaction (RT-PCR) tests, which aims to detect the presence of COVID-19. However, challenges with collection techniques and when in the disease lifecycle these tests are taken, can affect their reliability, highlighting a need for alternative methods of testing. Other testing methods exist, which involve testing the body’s own immune response to the presence of COVID-19, however these may also have their limitations. This systematic review and meta-analysis aimed to determine the effectiveness of testing the body’s own immune reaction for the presence of COVID-19. The results showed that testing the body’s immune reaction was effective, however if the person being tested is at an early stage in the disease, then it may be misdiagnosed. This study could be used by healthcare professionals to understand that the use of any type of COVID-19 testing may have its limitations, and although a person may test negative, there is still a possibility that they have the infection if symptoms exist
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.
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Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.
Catassi, GN, Pulvirenti, A, Monachesi, C, Catassi, C, Lionetti, E
Nutrients. 2021;14(1)
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Celiac disease typically develops within the first two years of life, however testing for it in children of this age is controversial. The immune test that is currently recommended for diagnosis in children, is both reliable and cost effective in adults, however, may not be suitable in this age group. This systematic review and meta-analysis aimed to determine whether extra immune testing is needed in children in addition to the more commonly recommended immune test. The results showed that based upon the 15 articles that were found, children with early celiac disease are possibly being mis-diagnosed due to a failure in the currently recommended testing not being sensitive enough. If a second immune test was added in combination with traditionally used tests, then it may ensure that diagnosis is more successful. This study could be used by healthcare practitioners to understand that current methods of testing for celiac disease in children, may give a false negative. To avoid this, it is recommended that children under two years of age have a combination of immune tests.
Abstract
The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); p < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); p = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.
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Oral birch pollen immunotherapy with apples: Results of a phase II clinical pilot study.
Nothegger, B, Reider, N, Covaciu, CE, Cova, V, Ahammer, L, Eidelpes, R, Unterhauser, J, Platzgummer, S, Raffeiner, E, Tollinger, M, et al
Immunity, inflammation and disease. 2021;9(2):503-511
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The prevalence of birch pollen allergy (BPA) has increased in recent years and has led to a rise in birch pollen-related food allergy (prFA). The current immunotherapy approach for BPA is to use birch pollen extract to attenuate the allergic response. While it has been successful for BPA, it has shown little to no effect on prFA, illuminating a current gap in the research. The aim of this pilot study was to assess the clinical efficacy of immunotherapy by daily apple consumption in developing permanent oral tolerance to apples and simultaneously to birch‐pollen. Sixteen participants consumed apples daily over an eight month period. Various allergy responses were measured during the peak birch pollen season. The results demonstrated continuous consumption of apples by BPA patients with prFA to apples could both improve prFA and birch-pollen induced allergic reactions. Based on these results, the authors conclude that oral immunotherapy with fresh apples is feasible and safe for the treatment of both BPA and birch prFA. As this was a small pilot study, a larger controlled trial is needed to confirm the potential of this treatment option in the clinical setting.
Abstract
BACKGROUND Seventy percent of patients suffering from birch pollen allergy (BPA) develop a pollen-related food allergy (prFA), especially to apples, due to a clinically relevant cross-reactivity between the major allergen in birch Bet v 1 and Mal d 1 in apples. Therefore allergen-specific immunotherapy with fresh apples (AITA) could be a promising natural treatment of both BPA and prFA. OBJECTIVE To assess the clinical efficacy of immunotherapy by daily apple consumption for patients with BPA and prFA. METHODS A daily defined increasing amount of selected cultivars (Red Moon®, Pink Lady®, Topaz, Golden Delicious) was continuously consumed by 16 patients (12 female; median age; 50; range, 23-68 years), leading to increased intake of allergen over a period of at least 8 months. Specific IgE and IgG4 to Bet v 1 and Mal d 1, conjunctival and oral provocation tests, skin reactivity, and the average daily rhinoconjunctivitis combined symptom and medication score (CSMS) were measured during the peak birch pollen season. RESULTS After 8 months of therapy, patients showed increased tolerance to apples (p < .001) and a decreased skin reactivity to apples. Oral allergy syndrome to other birch prFA than apple also decreased (p < .05). Moreover, daily rhinoconjunctivitis CSMS declined by 34% (p < .001), as did conjunctival reactivity to birch pollen extract by 27% (p < .01), while specific IgG4 to Mal d 1 and Bet v 1 increased (p < .01).
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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.