Elevated Antibody Levels Research Articles

Abstract #1402994: Unilateral Exophthalmos in A Patient with Hashitoxicosis: Case Report and Review of the Literature

Hashitoxicosis is a transient period of hyperthyroid state in a patient with Hashimoto thyroiditis. Ii is not common condition. Exophthalmos is usually bilateral disease commonly associated with Graves's hyperthyroidism. It rarely occurs in Hashimoto thyroiditis or hashitoxicosis. Unilateral exophthalmos is a less common presentation of Graves's ophthalmopathy. So, we present this case of a male with Hashimoto thyroiditis, who presented with unilateral exophthalmos and Hashitoxicosis. A 41-year-old male presented with protrusion of his right eye. He was diagnosed 9 months ago with Hashimoto thyroiditis based on clinical ground, laboratory tests and thyroid scan. His TSH was 18.5 (N 0.4- 4) and FT4 was 0.023 (N12-22). TPO was positive (Thyroid Peroxidase anti-bodies). Thyroid scan showed diffused homogeneous reduced uptake. He was started on Thyroxine 100ug/day. Six months later his thyroid function test on follows up showed features of subclinical hyperthyroidism. His Thyroxine was reduced gradually till it was stopped. Three months later, he developed palpitations, weight loss and noticed changes in his right eye. On examination he was toxic his pulse 100 bpm, right eye there is exophthalmos, lid retraction and lid lag. He has small goiter and no bruit. No pretibial myxedema or proximal myopathy. Laboratory tests showed suppressed THS 0,013 and high FT4 26.8. We diagnosed him as having Hashitoxicosis and started on Propranolol 20 mg three times daily. He did not improve and repeated TSH was 0.006 and FT4 was 46.3(12-22). Neomercazole was started at a dose of 30 mg/day, Over the next 6 months Neomercazole was tapered until the patient become hypothyroid and thyroxine was restarted. Currently he is on thyroxine 100ug and is doing well. However, the exophthalmos did not resolve completely. Hashimoto thyroiditis is the most common cause of hypothyroidism in Iodine sufficient areas. It is characterized by elevated levels of thyroid anti-bodies (Anti TPO antibodies are present in 90% of cases). Hashitoxicosis is the hyperthyroid phase in chronic autoimmune thyroiditis. it occurs due to the release of preformed thyroid hormones from the inflamed thyroid gland. The exact duration of the disease is not well described, in average it last less than 8 months. The term Hshitoxicosis sometimes used to describe an autoimmune thyroid disease overlap syndrome of Graves's disease and Hashimoto disease. The presentation of our patient was consistent with Hashitoxicosis. But due to his severe symptoms and development of exophthalmos we suspect overlap syndrome, so we started antithyroid medication. Wasniewska et al. investigated the outcome of Hashitoxicosis in 14 children. Due to more severe presentation, four patients required antithyroid medications as in our patient. A definitive resolution of hyperthyroidism was recorded 8.3- 6.3 months after the diagnosis, as in our patient who recovered over a period of 6 months. Graves's orbitopathy (GO) usually associated with Graves's hyperthyroidism, rarely occurs in hypo- or euthyroid state, unlike our patient who developed unilateral exophthalmos in hypothyroidism.

Determination of autoantibody repertoire in the mouse model of viral myocarditis and in patients with non-ischemic cardiomyopathy by PhIP-Seq

Abstract Various infectious and non-infectious agents can cause myocarditis that may lead to cardiomyopathy with viruses being the most common suspects. Mechanistically, autoantibodies have been demonstrated for various antigens, in animal models and dilated cardiomyopathy patients, but their role continues to be enigmatic. First, by using the Coxsackievirus B3 (CVB3) infection model in A/J mice, we applied PhIP-Seq, a high-throughput platform to evaluate antibodies for various antigens. The data revealed the identification of antibodies to 32 antigens that were not previously reported. By investigating the biological significance of a few select antigens, we noted that cytochrome c oxidase assembly factor 4 homolog (COA4)-reactive antibodies were generated only in mice infected with CVB3 but not in influenza-infected animals proving virus specificity for antibody reactivity to COA4. Further immunogenicity studies revealed that animals immunized with COA4 did not develop myocarditis, nor was the T cell response generated, implying that COA4 is unlikely to act as a bonafide autoantigen. Alternatively, the COA4-reactive antibodies may represent biomarkers of viral myocarditis. Second, using the PhIP-Seq platform, we investigated the antibody profiles of human sera obtained from 25 age-matched non-ischemic cardiomyopathy patients and healthy controls. The analysis revealed significantly elevated levels of antibodies to 33 antigens, and the detection of the major candidates is being analyzed by ELISA as a secondary assay. Overall, our data suggest that the PhIP-Seq allows us to comprehensively analyze antibody repertoires that may lead to the identification of novel autoantibodies or their use as biomarkers. This work was supported in part by the institutional funds from the University of Nebraska-Lincoln (J.R.), the Transformational Grant 18TPA34170206 from the American Heart Association (J.R.), and the National Institutes of Health grants R01 HL114669 (J.R), R01 GM136724 (H.B.L.).

Antibodies against Histoplasma capsulatum and Aspergillus fumigatus among chronic TB patients in Indonesia: a cross-sectional study.

Chronic pulmonary fungal infections may occur in patients with previous history of pulmonary tuberculosis (TB), and are often clinically misclassified as TB, especially when bacteriological confirmation for Mycobacterium tuberculosis is absent. In this study, we investigated the prevalence of antibody against Histoplasma capsulatum and Aspergillus fumigatus in patients with confirmed and clinically chronic TB. Antibodies against H. capsulatum and A. fumigatus were measured from serum samples using enzyme-linked immunosorbent assay (ELISA). The presence M. tuberculosis in sputum was confirmed using smear microscopy, GeneXpert MTB/RIF assay, or culture. Antibodies against H. capsulatum and A. fumigatus were elevated in 16.9% and 26.9% of bacteriologically confirmed chronic TB patients, and 12.1% and 18.2% in those without bacteriological confirmation, respectively. Approximately one-third of patients who had positive anti-Histoplasma antibody also had elevated levels of antibody against Aspergillus fumigatus (P<.001). Our study highlights the importance of chronic pulmonary fungal infection in post-TB patients with recurrent respiratory symptoms.

Levels of antibodies to adalimumab in children with juvenile idiopathic arthritis at different stages of treatment

Background. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatological diseases of childhood. The central place in the problem of JIA belongs to the question of treatment the timeliness and adequacy of which determine the disease prognosis and, in fact, the entire future of the child. Immunobiological therapy can cause stable clinical and laboratory remission, as well as stop the further progression of structural changes, affecting the pathogenetic link of idiopathic arthritis. But the lack of response to therapy or a decrease in its effectiveness remains a fairly common problem and, in many cases, can be caused by the immunogenicity of immunobiological drugs, especially in case of treatment with tumor necrosis factor inhibitors. Aim of the work: to study the level of antibodies to adalimumab in children with juvenile idiopathic arthritis at different stages of treatment for analysis of immunogenicity. Materials and methods. The concentration of antibodies to adalimumab in 80 serum samples from patients with JIA was studied and evaluated, treatment effectiveness and adverse events were analyzed in 56 patients with JIA at different stages of therapy. Two groups were identified. The first one included 24 patients who had at least a 6-month break in adalimumab administration for non-medical reasons during which treatment was continued with methotrexate with periodic intra-articular injection of glucocorticoids. The level of antibodies to adalimumab was evaluated before the break and 1 month after the reinitiation of adalimumab administration. The second group consisted of 32 children who continued adalimumab without a break during treatment. Disease activity was measured using JADAS-27. Antibodies to adalimumab were detected by enzyme-linked immunosorbent assay. Results. During the examination, an elevated level of antibodies to adalimumab was detected in 10 of 24 serum samples (42 %) before non-medical withdrawal in group I. Among the results of group II, elevated levels of antibodies to adalimumab were found in 12 samples, which was 38 %. The correlation analysis revealed direct statistically significant relationships of moderate strength between the level of antibodies to adalimumab and the indicator of inflammatory activity on JADAS-27 (Spearman’s r = 0.39, p &lt; 0.05), as well as between the level of antibodies and disease duration (Spearman’s r = 0.32, p &lt; 0.05). Conclusions. Monitoring serum antibodies to adalimumab is informative for the correct interpretation of treatment effectiveness and the course of the disease with immunobiological treatment, as it may improve understanding of the clinical consequences of continued therapy, help prevent adalimumab immunogenicity, develop follow-up strategies and, as a result, can affect a long-term outcome of treatment for JIA.

Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model

Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the 2016 Zika virus (ZIKV) outbreak, rapid availability of vaccines can prove critical in reducing widespread disease burden. The recent successes of mRNA vaccines support their evaluation in pregnant animal models to justify their use in neonatal settings. Here we evaluated immunogenicity of self-amplifying replicon (repRNA) vaccines, delivered with our clinical-stage LION nanoparticle formulation, in pregnant rabbits using ZIKV and HIV-1 as model disease targets. We showed that LION/repRNA vaccines induced robust antigen-specific antibody responses in adult pregnant rabbits that passively transferred to newborn kits in utero. Using a matrixed study design, we further elucidate the effect of vaccination in kits on the presence of pre-existing maternal antibodies. Our findings showed that timing of maternal vaccination is critical in maximizing in utero antibody transfer, and subsequent vaccination in newbornsmaintained elevated antibody levels compared with no vaccination. Overall, our results support further development of the LION/repRNA vaccine platform for maternal and neonatal settings.

Hospitalized patients with positive antiphospholipid antibodies who have low complement levels are at increased risk for death—a retrospective cohort study

To investigate whether low complement levels can predict worse outcomes in patients hospitalized with positive anti-phospholipid antibodies. This was a retrospective cohort study. We obtained demographics, laboratory, and prognostic data of all consecutive patients hospitalized between 2007 and 2021, for whatever reason, with at least one positively abnormal anti-phospholipid antibody, who were also tested for complement levels (C3 or C4). We then compared the rates of long-term mortality, 1-year mortality, deep vein thrombosis, and pulmonary emboli between groups of low complement and normal complement levels. Multivariate analysis was used to control for levels of clinical and laboratory confounders. We identified 32,286 patients tested for anti-phospholipid antibodies. Of those patients, 6800 tested positive for at least one anti-phospholipid antibody and had a documented complement level. Significant higher mortality rates were found in the low complement group, with an odds ratio for mortality (OR 1.93 CI 1.63-2.27 p < .001). Deep vein thrombosis and pulmonary emboli rates were similar. Multivariate analysis confirmed that low complement was an independent predictor for mortality after controlling for age, sex, dyslipidemia, chronic heart failure (CHF), chronic kidney disease (CKD), and anemia. Our study results indicate that low complement is associated with significantly higher mortality rates in admitted patients with elevated levels of anti-phospholipid antibodies. This finding correlates with recent literature suggesting a vital role for complement activation in anti-phospholipid syndrome.

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies

ObjectiveDetection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. MethodsWe performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb−) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. ResultsPatients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. ConclusionWe conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

B lymphocyte responses in Parkinson's disease and their possible significance in disease progression.

Inflammation contributes to Parkinson's disease pathogenesis. We hypothesized that B lymphocytes are involved in Parkinson's disease progression. We measured antibodies to alpha-synuclein and tau in serum from patients with rapid eye movement sleep behaviour disorder (n = 79), early Parkinson's disease (n = 50) and matched controls (n = 50). Rapid eye movement sleep behaviour disorder cases were stratified by risk of progression to Parkinson's disease (low risk = 30, high risk = 49). We also measured B-cell activating factor of the tumour necrosis factor receptor family, C-reactive protein and total immunoglobulin G. We found elevated levels of antibodies to alpha-synuclein fibrils in rapid eye movement sleep behaviour disorder patients at high risk of Parkinson's disease conversion (ANOVA, P < 0.001) and lower S129D peptide-specific antibodies in those at low risk (ANOVA, P < 0.001). An early humoral response to alpha-synuclein is therefore detectable prior to the development of Parkinson's disease. Peripheral B lymphocyte phenotyping using flow cytometry in early Parkinson's disease patients and matched controls (n = 41 per group) revealed reduced B cells in Parkinson's disease, particularly in those at higher risk of developing an early dementia [t(3) = 2.87, P = 0.01]. Patients with a greater proportion of regulatory B cells had better motor scores [F(4,24) = 3.612, P = 0.019], suggesting they have a protective role in Parkinson's disease. In contrast, B cells isolated from Parkinson's disease patients at higher risk of dementia had greater cytokine (interleukin 6 and interleukin 10) responses following in vitro stimulation. We assessed peripheral blood lymphocytes in alpha-synuclein transgenic mouse models of Parkinson's disease: they also had reduced B cells, suggesting this is related to alpha-synuclein pathology. In a toxin-based mouse model of Parkinson's disease, B-cell deficiency or depletion resulted in worse pathological and behavioural outcomes, supporting the conclusion that B cells play an early protective role in dopaminergic cell loss. In conclusion, we found changes in the B-cell compartment associated with risk of disease progression in rapid eye movement sleep behaviour disorder (higher alpha-synuclein antibodies) and early Parkinson's disease (lower levels of B lymphocytes that were more reactive to stimulation). Regulatory B cells play a protective role in a mouse model, potentially by attenuating inflammation and dopaminergic cell loss. B cells are therefore likely to be involved in the pathogenesis of Parkinson's disease, albeit in a complex way, and thus warrant consideration as a therapeutic target.

Pre-existing Fc profiles shape the evolution of neutralizing antibody breadth following influenza vaccination

Under the ever-present threat of a pandemic influenza strain, the evolution of a broadly reactive, neutralizing, functional, humoral immune response may hold the key to protection against both circulating and emerging influenza strains. We apply a systems approach to profile hemagglutinin- and neuraminidase-specific humoral signatures that track with the evolution of broad immunity in a cohort of vaccinated individuals and validate these findings in a second longitudinal cohort. Multivariate analysis reveals the presence of a unique pre-existing Fcγ-receptor-binding antibody profile in individuals that evolved broadly reactive hemagglutination inhibition activity (HAI), marked by the presence of elevated levels of pre-existing FCGR2B-binding antibodies. Moreover, vaccination with FCGR2B-binding antibody-opsonized influenza results in enhanced antibody titers and HAI activity in a murine model. Together, these data suggest that pre-existing FCGR2B binding antibodies are a key correlate of the evolution of broadly protective influenza-specific antibodies, providing insight for the design of next-generation influenza vaccines.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC]=0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC=0.85, 95% CI=0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Association between the quality of plant-based diets and periodontitis in the U.S. general population.

To investigate the relationship between plant-based diet indices (PDIs) and periodontitis and serum IgG antibodies against periodontopathogens in the U.S. We analysed cross-sectional data on 5651 participants ≥40 years of age from the Third National Health and Nutrition Examination Survey. Food frequency questionnaire data were used to calculate the overall PDI, healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Periodontitis was defined using a half-reduced Centers for Disease Control and Prevention and American Academy of Periodontology case definition. Serum antibodies against 19 periodontopathogens were used to classify the population into two subgroups using hierarchical clustering. Survey-weighted multivariable logistic regressions were applied to assess the associations of PDI/hPDI/uPDI z-scores with periodontitis and hierarchical clusters after adjusting for potential confounders. A total of 2841 (50.3%) participants were defined as having moderate/severe periodontitis. The overall PDI z-score was not significantly associated with the clinical and bacterial markers of periodontitis. By considering the healthiness of plant foods, we observed an inverse association between hPDI z-score and periodontitis (odds ratio [OR]=0.925, 95% confidence interval [CI]:0.860-0.995). In contrast, higher uPDI z-score (adherence to unhealthful plant foods) might increase the risk of periodontitis (OR=1.100; 95% CI: 1.043-1.161). Regarding antibodies against periodontopathogens, the participants in cluster 2 had higher periodontal antibodies than those in cluster 1. The hPDI z-score was positively associated with cluster 2 (OR=1.192; 95% CI: 1.112-1.278). In contrast, an inverse association between uPDI z-score and cluster 2 was found (OR=0.834; 95% CI: 0.775-0.896). Plant-based diets were associated with periodontitis, depending on their quality. A healthy plant-based diet was inversely related to an increased risk of periodontitis but positively related to elevated antibody levels against periodontopathogens. For an unhealthy plant-based diet, the opposite trends were observed.

A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis

Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice. However, one of the antibodies, clone E4, protected mice from antibody-induced arthritis. E4 showed a binding pattern restricted to skin, macrophages and dendritic cells in lymphoid tissue, and cartilage derived from mouse and human arthritic joints. Proteomic analysis confirmed that E4 strongly binds to macrophages and certain RA synovial fluid proteins such as α-enolase. The protective effect of E4 was epitope-specific and dependent on the interaction between E4-citrullinated α-enolase immune complexes with FCGR2B on macrophages, resulting in increased IL-10 secretion and reduced osteoclastogenesis. These findings suggest that a subset of ACPAs have therapeutic potential in RA.

Assessment of Reactivity to the Administration of the mRNA Vaccine after Six Months of Observation.

The fast spread of the SARS-CoV-2 virus accelerated efforts to create an effective vaccine, and a novel mRNA vaccine was the first to appear effective. Scientific evidence regarding mRNA vaccination is limited; therefore, understanding how the immune system responds to an mRNA vaccine is critical. Our study was aimed at a long-term analysis of the presence and maintenance of the immune response using the chemiluminescent method by analyzing the level of IgG antibodies in vaccinated people who were and were not infected with the SARS-CoV-2 virus. Healthcare workers with a history of COVID-19 or who were naïve to the infection were recruited for this study and administered two subsequent doses of the Comirnaty vaccine. IgG SRBD antibody levels were evaluated every month for six consecutive months using the chemiluminescent immunoassay (CLIA). A total of 149 individuals were recruited for this study, 68 had evidence of past COVID-19 infection, with 63 exhibiting elevated IgG SRBD antibody levels at initial evaluation. Statistically significant differences were observed between COVID-19 convalescents and non-convalescents at all study time points, with the convalescent group consequently representing higher antibody levels. COVID-19 convalescents showed a stronger immune response to the vaccine after the first dose. This group exhibited higher IgG levels in all examinations during the observation period. The natural waning of antibody levels can be observed within six months. A booster vaccination may be required. No serious side effects were observed.

Leishmania donovani induces CD300a expression to dampen effector properties of CD11c+ dendritic and antigen activated CD8+ T cells

CD8+ T cells are an important regiment of adaptive immunity that play a decisive role in elimination of many species of Leishmania parasite from the host. In visceral leishmaniasis, caused by L. donovani, the loss of CD8+ T cells function has been found associated with augmented pathogenesis. The factors determining CD8+ T cells activation and function against Leishmania antigens are largely unknown. In this study, we investigated the role of an immune inhibitory receptor, CD300a, on the effector properties of dendritic cells and CD8+ T cells. We observed that the Leishmania regulates the effectors function of CD8+ T cells by increasing CD300a expression on CD11c+ dendritic cells. The abrogation of CD300a signaling in parasites infected animals induced CD8+ T cell abilities to produce IFN-γ, TNF-α and also helped them to acquire desired multifunctionality. The CD300a receptor blocking also enhanced the number of CD8+ T cells memory phenotypes at the early days of infection, suggesting its potential beneficial role in vaccine induced immunity. We also observed significantly enhanced levels of pro-inflammatory cytokines in the spleen of CD300a blocked infected animals with concomitant reduced spleen parasite load. Additionally, the abrogation of CD300a signals in the infected animals helped in establishing Th1 type protective humoral immunity with significantly elevated levels of IgG2a antibodies. Since CD8+ T cells are an important determinant of vaccine induced immunity against leishmaniasis, the findings corroborate the potential of CD300a in vaccine induced immunity and thus require further attention.

Тяжелое течение целиакии, осложненной стрессовой гипергликемией

This article presents a clinical case of lately diagnosed celiac disease complicated by stress-induced hyperglycemia. A 2-yearold patient was admitted to the intensive care unit of the Republican Specialized Scientific and Practical Medical Center of Pediatrics with severe protein-energy malnutrition, lethargy, abdominal bloating, and constipation. On admission, the child had hypoproteinemia, hypoalbuminemia, blood glucose levels up to 11.7 mmol/L, and anemia. On the third day of illness, blood glucose levels reached 16 mmol/L, which was considered as stress-induced hyperglycemia. Glucose levels were reduced by insulin injections on day 9. Celiac disease was suspected based on complaints, anamnestic, clinical and laboratory findings. Examination revealed elevated levels of IgA antibodies to tissue transglutaminase, exceeding the reference values 15 times. Genetic study confirmed the presence of predisposition to the disease. Catamnestic follow-up demonstrated a positive effect of a gluten-free diet. This is the first description of a typical form of celiac disease with late diagnosis and complications such as stress-induced hyperglycemia, respiratory failure, protein-energy malnutrition, and protein-losing enteropathy. Early diagnosis is very important to prevent long-term complications. Key words: children, malabsorption, celiac disease, stress hyperglycemia, protein-losing enteropathy

Rare Complications of Celiac Disease: Clinicopathologic Features

Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation. The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.

The role of a conjunctival biopsy in the diagnosis of eosinophilic granulomatosis with polyangiitis with ocular involvement

A 33-year-old Asian man presented with redness, swelling, and blurring of vision in both eyes for 1 month associated with headache and pain. The patient had a history of allergic rhinitis with a progressive hearing loss for 3 months, followed by bell's palsy. Given his elevated serum cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as computed tomography head, orbit, and peripheral nervous system that showed marked bilateral mastoiditis with opacification of the right middle ear canal and enlargement of the bilateral lacrimal gland, the suspicion of small vessel vasculitis with ocular and ear involvement was high. Because there was no significant lung or kidney involvement, a conjunctival biopsy was attempted, which revealed small capillaries surrounded by eosinophils and plasma cells. Because there are no validated diagnostic tests for eosinophilic granulomatosis with polyangiitis (EGPA), a conjunctival biopsy can be valuable and minimally invasive in the early diagnosis and treatment of small vessel vasculitis.

SERUM ANTIBODIES AGAINST GroEL AS AN ADDITIONAL RISK BIOMARKER OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY.

Thelevel of heat shock protein 60 (Hsp60) is elevated in tumor cells compared with normal prostate epithelium. Hsp60is involved in tumor growth, invasion, and metastasis and is considered as a biomarker for cancer diagnosis and prognosis. To study thelevel of antibodies against prokaryotic homolog of human Hsp60 (GroEL) in prostate cancer (PCa) patients as an additional risk marker for theprediction of biochemical recurrence after radical prostatectomy (RP). A total of 55patients with localized and locally advanced PCa, who had undergone RP between July 2013and May 2014were enrolled. Level of antibodies to GroEL and human Hsp60was determined by enzyme-linked immunosorbent assay before surgery. Serum samples of blood donors with low reactivity to GroEL and human Hsp60were used as controls. Therelationship between IgG antibodies against bacterial Hsp60and human Hsp60and clinicopathological features were analyzed. Thebiochemical recurrence (BCR) free survival rate was estimated by theKaplan - Meier method. Theunivariate and multivariate Cox regression models were used to evaluate therisk factors of BCR-free survival rate. There were significant differences in anti-GroEL IgG levels between control and PCa patients while no significant differences in anti-human Hsp60IgG levels between control and PCa patients were detected. During thefollow-up period, 40/55 (72.7%) patients developed BCR. Thetime from surgery to BCR was from 18to 72months. Elevated IgG antibodies against bacterial Hsp60in patients who had undergone RP were associated with early occurrence of biochemical relapse and lower 5-year BCR-free survival rate respectively (p < 0.001). Themultivariate analysis indicated that IgG to GroEL (hazard ratio = 2.465; 95% confidence interval: 1.311-4.634, p < 0.05) could be independent prognostic factor in thepatients who had developed BCR. Elevated levels of IgG antibodies against GroEL before surgery can predict early occurrence of BCR after RP and can serve as an additional independent risk biomarker of a BCR after RP.

Cardiopulmonary Bypass Surgery in a Patient with Unexpected Heparin-Induced Thrombocytopenia.

We report a case of a 77-year-old woman with massive pulmonary embolism associated with heparin-induced thrombocytopenia. Before developing a pulmonary embolism, the patient underwent gastrectomy due to gastric cancer and received subcutaneous heparin calcium for deep venous thrombosis prophylaxis for 5 d. Then, thrombectomy with cardiopulmonary bypass using full heparinization was successfully performed. The patient was definitively diagnosed with this condition postoperatively, based on elevated serum antibody levels, in addition to pre- and postoperative thrombocytopenia and thrombosis. Intravenous heparin therapy was switched to argatroban. Although it is uncommon, clinicians should consider this condition in patients with a history of heparin exposure.

Severe Raynaud’s phenomenon from ethosuximide raised concern over possible onset of systemic vasculitis: a case report

BackgroundEthosuximide and other anti-epileptic drugs have been reported to cause idiosyncratic reactions such as lupus-like syndromes, with elevated antinuclear antibody (ANA) levels. Herein, we present a case of a girl who developed a very severe Raynaud’s phenomenon reaction and anti-Scl-70 antibodies related to treatment with ethosuximide, due to juvenile absence epilepsy (JAE).Case presentationA 12-year-old girl was diagnosed with JAE and treatment with ethosuximide was initiated. Two and a half months later her fingers, digits II–V bilaterally, began to ache and were discolored, alternatingly white, blue, or normal-colored. Two weeks later, her fingers were bluish-black, aching severely, almost continuously. The family sought medical advice. Ethosuximide was halted and due to the severe symptoms, treatment with both prednisolone and intravenous iloprost was commenced. Laboratory tests revealed high ANA levels with anti-Scl-70 pattern and confirmed anti-Scl-70 antibodies. After a few weeks, she started to improve and the symptoms slowly decreased over five months. Anti-Scl-70 was still detectable four months after onset of symptoms, though she was much improved. After eleven months, repeated ANA analyses were completely negative.ConclusionAlthough extremely rare, it is important to recognize that severe Raynaud’s phenomenon, threatening peripheral digital circulation, may occur as an idiosyncratic reaction to ethosuximide, raising concern over possible onset of vasculitis.