The Prognostic Value of Anti-PLA2R Antibodies Levels in Primary Membranous Nephropathy.

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50-71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35-183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients.

Outcomes of ICU patients treated with intravenous immunoglobulin for sepsis or autoimmune diseases.

OBJECTIVES: To evaluate the outcomes of hospitalized patients in two intensive care units (ICU) treated with intravenous immunoglobulin (IVIg) added to standard-of-care therapy. The indications for IVIg therapy were sepsis or autoimmune disease. METHODS: We conducted a retrospective study involving adult patients with sepsis and autoimmune diseases, who received IVIg in the ICU at Wolfson and Sheba Medical Centers. A predefined chart was compiled on Excel to include a complete demographic collection, patient comorbidities, chronic medication use, disease severity scores (Charlson Comorbidity Index; SOFA and APACHE II index scores), indication and dosage of IVIg administration, duration of hospitalization and mortality rates. RESULTS: Patients (n - 111) were divided into 2 groups: patients with sepsis only (n-67) and patients with autoimmune disease only (n-44). Septic patients had a shorter ICU stay, received IVIg early, and had reduced mortality if treated with high dose IVIg. Patients with autoimmune diseases did not have a favorable outcome despite IVIg treatment. In this group, IVIg was administered later than in the sepsis group. CONCLUSIONS: IVIg therapy improved the outcomes for ICU patients with sepsis.

Tumor-like Lesions in Patients with Granulomatosis with Polyangiitis: A Case Series.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue. OBJECTIVES: To report three unique cases of GPA presenting with tumor-like lesions in various organs. METHODS: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass. RESULTS: The patients were treated successfully with rituximab. CONCLUSIONS: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener's granulomatosis.

The Utility of 18FDG-PET/CT in Diagnosing Fever of Unknown Origin: The Experience of a Large Tertiary Medical Center.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis-A Cross-Sectional Study.

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case-control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student's t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan-Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.

The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO-positive IgG on fetal loss in naïve mice.

PROBLEM: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies. AIM: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. METHOD OF STUDY: Naïve ICR female mice, infused intravenously with 100 µg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples. CONCLUSION: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.

Seroprevalences of autoantibodies and anti-infectious antibodies among Ghana's healthy population.

Autoantibodies, which are antibodies that target self-epitopes, have considerable diagnostic, prognostic and predictive value in specific autoimmune diseases. Various infectious agents have been linked via numerous mechanisms to the formation of different autoantibodies. Therefore, estimating the prevalence of autoantibodies and anti-infectious antibodies in different populations is of high importance. Different genetic and environmental pressures, such as these found in Ghana's different geographical provinces, may affect the prevalence of autoantibodies. In this study, we assessed the seroprevalence of a diverse panel of autoantibodies and anti-infectious antibodies among the healthy Ghanaian population and investigated possible environmental and genetic predispositions for autoantibodies and autoimmunity. The sera of 406 healthy individuals were obtained from Greater Accra, Upper West, Eastern and Volta regions. Multiplexed assay and chemiluminescent immunoassay techniques were utilized to assess the presence of a panel of autoantibodies and anti-infectious antibodies. We found a high prevalence of anti-HSV-1 IgG (91-100%), anti-EBNA IgG (81-93%) and anti-EBV-VCA IgG (97-100%) antibodies. The prevalence of ANA (at least one of: anti-dsDNA; anti-chromatin; anti-ribosomal-P; anti-Ro/SSA; anti-La/SSB; anti-centromere B; anti-Sm; anti-Sm/RNP; anti-Scl-70; anti-Jo1; anti-DFS70) was estimated at 14%. An inverse association between anti-HSV-2 antibodies and ANA (p = 0.044; adjusted OR = 0.398; CI [0.162-0.975]) was found, after adjusting for differences in gender, age, and familial history of autoimmune diseases. A trend towards reduced seroprevalence of anti-dsDNA antibodies among subjects who were positive for anti-HSV-2 antibodies was also noted (p = 0.1). In conclusion, the inverse association between anti-HSV-2 antibodies and ANA positivity suggests a possible protective role of HSV-2 infection against autoimmunity.

Mortality among Patients with Giant Cell Arteritis: A Large-scale Population-based Cohort Study.

OBJECTIVE: Studies regarding mortality among patients with giant cell arteritis (GCA) have yielded conflicting results. Thus in this large population-based study we aimed to examine whether GCA is associated with increased mortality, and if so, the effect of age at diagnosis and sex on the association. METHODS: We used the medical database of Clalit Health Services for this retrospective cohort study. Followup was from January 1, 2002, and continued until death or end of followup on September 1, 2018. Incident GCA patients were compared with age- and sex-matched controls. Estimated median survival times were calculated using the Kaplan-Meier method. HR for all-cause mortality were obtained by the Cox proportional hazard model, adjusted for sociodemographic variables and cardiovascular risk factors. RESULTS: The study included 7294 patients with GCA and 33,688 controls. The mean age at start of followup was 72.1 ± 9.9 years with 69.2% females. Estimated median survival time was 13.1 years (95% CI 12.6-13.5) in patients with GCA compared with 14.4 years (95% CI 14.1-14.6) in controls (p < 0.001). The multivariate analysis demonstrated increased mortality risk in the first 2 years after diagnosis (HR 1.14, 95% CI 1.04-1.25) and > 10 years after diagnosis (HR 1.14, 95% CI 1.02-1.3). The mortality risk was higher in patients diagnosed at ≤ 70 years of age [HR 1.5 (95% CI 1.14-1.99) 0-2 yrs; HR 1.38 (95% CI 1.1-1.7) > 10 yrs]. CONCLUSION: Patients with GCA have a minor decrease in longterm survival compared to age- and sex-matched controls. The seen difference is due to excess mortality in the first 2 years, and > 10 years after diagnosis. Patients diagnosed ≤ 70 years of age are at greater risk.

The coexistence of gout in ankylosing spondylitis patients: a case control study.

Ankylosing spondylitis (AS) and gout are common inflammatory arthropathies. It had been claimed previously that the two conditions rarely coexist. The aim of this study was to compare the prevalence of gout in a population of AS patients to its prevalence in the general population. To conduct this population-based case-control study, data of adult patients with a physician diagnosis of AS were retrieved from the database of the largest health-care provider organization in Israel, Clalit Health Services. For each patient with AS, five age- and sex-matched subjects without AS were randomly selected from the same database. Different parameters including the existence of gout, hypertension, body mass index, socioeconomic status, and smoking were evaluated in both the AS and the control groups. The study included 3763 patients with AS and 19,214 controls. The proportion of gout in the AS group was higher than in the control group: 73 subjects in the AS group had gout, while only 107 subjects in the non-AS group had gout (1.94% and 0.56%, respectively, OR 3.53, P < 0.001). Logistic regression adjusting for possible confounding variables found that AS was independently associated with gout (OR 1.41, P = 0.037). Our study suggests that gout is not less common in AS patients in comparison with the general population, and that it might even be more common in AS patients.

Algorithm for antinuclear antibodies in subjects with clinical suspicion of autoimmune diseases.

OBJECTIVES: Antinuclear antibodies (ANA) are fundamental in the diagnosis of systemic autoimmune rheumatic diseases (SARDs). Different assays for ANA screening are available, such as indirect immunofluorescence (IIF) on HEp-2 cells and Multiplex fluorescent immunoassay (MFI). This study aimed to clarify the importance of ANA detected only by IIF in the future development of SARDs and to recommend a laboratory algorithm that integrates the available diagnostic approaches to optimise the diagnosis of ANA IIF+MFI- subjects. METHODS: A total of 9,291 subjects with clinical suspicion of SARDs were evaluated for ANA by IIF and MFI. One hundred and ninety-eight subjects (2.1%) were ANA IIF+MFI-, who were followed up for 2 years. ANA were evaluated using IIF on HEp-2 cells and MFI on the BioPlex 2200. RESULTS: The ANA IIF+MFI- cohort included 106 subjects with SARDs, 26 subject with other autoimmune diseases (not-SARDs) and 66 subjects with minor symptoms or ANA requested in check-ups. Only 94 subjects underwent re-evaluation. After a 2-year follow-up, most re-evaluated subjects (51 patients) became ANA negative for both assays (mainly rheumatoid arthritis, polymyalgia and inflammatory bowel disease patients) and 35 subjects remained ANA IIF+MFI- (principally systemic sclerosis and systemic lupus erythematosus patients). A new algorithm for ANA evaluation was suggested. CONCLUSIONS: According to the proposed algorithm, ANA IIF+MFI- subjects should be screened by an alternative solid-phase assay such as line-immunoassay or ELISA.

Acute onset of psoriatic spondyloarthritis as a new manifestation of post-streptococcal reactive arthritis: a case series.

Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7-10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection. KEY POINTS: • Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7--10 days of a confirmed streptococcal infection and progressed to full blown chronic disease. • Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

Zika autoimmunity and Guillain-Barré syndrome.

PURPOSE OF REVIEW: To summarize the recent data regarding Guillain-Barré syndrome (GBS) as an autoimmune disorder following infection with Zika virus (ZIKV) infection, including the proposed pathogenic mechanisms and the role of autoantibodies. RECENT FINDINGS: The loss of self-tolerance that leads to autoimmune diseases is a multifactorial process that may be illustrated as 'the mosaic of autoimmunity'. Infectious agents may contribute to the development of autoimmunity by several proposed mechanisms. One of the central mechanisms is molecular mimicry, which is also the most plausible mechanism in the case of ZIKV-induced autoimmune disorders.A recent meta-analysis found a low prevalence of GBS associated with ZIKV infection. Nevertheless, the estimated cost of illness for patients with GBS associated with ZIKV are tremendous and exceed 4.7 million dollars per year in Brazil alone. SUMMARY: Currently, there is sufficient data to indicate that ZIKV infection is one of many triggers and factors that may contribute to the development GBS. Thus, it is advised to evaluate and determine ZIKV exposure and infection in the management of potential GBS patients.

Mortality of patients with rheumatoid arthritis requiring intensive care: a single-center retrospective study.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at a high risk for life-threatening conditions requiring admission to the intensive care unit (ICU), but the data regarding the outcomes of these patients is limited. The present study investigated the clinical characteristics and outcomes of RA patients admitted to an ICU. METHODS: This retrospective cohort study included RA patients admitted to the general ICU of the Sheba Medical Center during 2002-2018. The main outcome was 30-day mortality. Using Student's t test, χ2, and multivariable analyses, we compared the demographic, clinical, and laboratory parameters of the survivors and the non-survivors. Figures with p value < 0.05 were considered statistically significant. RESULTS: Forty-three RA patients were admitted to the ICU during the study period (mean age, 64.0 ± 13.1 years; 74.4% female). The leading causes of ICU admission were infection (72.1%), respiratory failure (72.1%), renal failure (60.5%), and septic shock (55.8%). The 30-day mortality rate was 34.9%, with infection (9/15, 60%) as the most frequent cause. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 19.7 ± 12.5 and 7.0 ± 4.5, respectively. Multivariable analysis showed that heart failure (p = 0.023), liver failure (p = 0.012), SOFA score (p = 0.007), and vasopressor treatment in ICU (p = 0.039) were significantly associated with overall mortality. SOFA score was linked with overall mortality (area under the curve (AUC) = 0.781 ± 0.085, p = 0.003) and mortality from respiratory failure (AUC = 0.861 ± 0.075, p = 0.002), while APACHE II score was only correlated with mortality from infection (AUC = 0.735 ± 0.082, p = 0.032). CONCLUSIONS: Our study demonstrated a relatively high mortality rate among RA patients who were admitted to the general ICU. RA patients with risk factors such as heart failure, liver failure, elevated SOFA score, and vasopressor treatment in ICU should be promptly identified and treated accordingly. Key Points • The 30-day mortality rate of patients with RA that were admitted to the general ICU of a tertiary hospital was 34.9%. • The most common causes of ICU admission among patients with RA were infections and respiratory failure. Infections were the most common cause of death among these patients. • Patients with RA that present to the ICU with heart failure, liver failure, elevated SOFA score, and/or require vasopressor treatment in ICU should be promptly identified and treated accordingly.

Anakinra in idiopathic recurrent pericarditis refractory to immunosuppressive therapy; a preliminary experience in seven patients.

BACKGROUND: Approximately 5% of idiopathic recurrent pericarditis (IRP) patients are refractory or intolerant to NSAIDs, Colchicine and corticosteroids. The empiric treatment approach for these patients includes immunosuppression with Azathioprine (AZA) or immunomodulation with intravenous human immunoglobulin (IVIG). We assessed the efficacy and safety of long-term Anakinra treatment in refractory IRP patients after failure of prior immunosuppressive therapy and/or failure of IVIG. METHODS: Clinical data of seven IRP patients were retrospectively analyzed. Treatment efficacy was determined by decrease of IRP recurrence and by the ability to withdraw or taper corticosteroids without a relapse. Safety was assessed by the occurrence of adverse events. RESULTS: 7 IRP patients (4 male, median age 41) with a median disease duration of 4 years (range: 1.25-9 years) were treated with Anakinra (median treatment duration: 20 months). All patients were resistant or intolerant to NSAIDs, Prednisone, Colchicine and at least one immunosuppressive or immunomodulatory drug such as AZA, Methotrexate, Plaquenil, or IVIG. The median number of recurrences before Anakinra was 6 (range: 4-7) and all patients were corticosteroid-dependent and had steroid-related side effects. After initiation of Anakinra, none of the patients had IRP relapse. Prednisone was tapered down to 5 mg/day or less in all patients. Four patients discontinued prednisone altogether. No significant adverse effects have occurred as a result of Anakinra treatment and all patients continued treatment after the study period. CONCLUSION: Long-term Anakinra is a rapid-acting, efficient and safe steroid sparing agent even for patients with IRP refractory to previous immunosuppressive and/or immunomodulatory agents.

Oral administration of Domain-I of beta-2glycoprotein-I induces immunological tolerance in experimental murine antiphospholipid syndrome.

It is well established that the humoral immunity in antiphospholipid syndrome (APS) is presented by circulating pathogenic anti-ß2GPI autoantibodies targeting mainly domain I of the ß2GPI protein, playing a major role in the disease pathogenesis. Previously, we have demonstrated that treatment of experimental APS mice with tolerogenic dendritic cells loaded with domain-I was more efficient in tolerance induction than with the whole molecule or domain-V. In the current study we had orally administered a domain-I derivative of the ß2GPI molecule, as a new therapeutic approach to induce oral tolerance in this mouse model of APS. BALB/c mice immunized with ß2GPI, were fed with either domain-I, domain-V derivative or the complete ß2GPI protein. ß2GPI immunized mice developed experimental APS which were fed with domain-I significantly had decreased fetal loss (p < 0.004), a lower size of thrombi (p < 0.001) and lower circulating anti-ß2GPI Abs in comparison to mice fed with domain-V or PBS (p < 0.002). Likewise, Domain-I fed mice had a lowered inflammatory response, exhibited by decreased expression of inflammatory cytokines (IFNγ, IL-6, IL-17) and elevated production of IL-10 anti-inflammatory cytokine by splenocytes. Moreover, the anti-inflammatory response in the domain-I fed APS mice was associated with increased circulating miRNA variations (155, 146, 182, 98) by RT-PCR, which are associated with immunomodulation of the immune network. We propose that oral tolerance with domain-I can be a novel therapy for patients with APS.

Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays.

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by immune-mediated muscular lesions that may be associated with extra-muscular manifestations involving skin, lungs, heart or joints. Four main groups of IIM can be distinguished: dermatomyositis (DM), overlap myositis including mainly anti-synthetase syndrome (ASS), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Myositis-specific autoantibodies (MSA) are increasingly recognized as valuable tools for diagnosis, classification and prognosis of IIM. For example, ASS is associated with anti-aminoacyl tRNA synthetase antibodies (anti-Jo-1, PL-7, PL-12, …), IMNM with anti-SRP and anti-HMGCR; IBM with anti-cytosolic 5'nucleotidase 1A (cN1A), and DM with anti-Mi-2, anti-MDA-5, anti-TIF-1γ, anti-NXP-2 and anti-SAE. Moreover, anti-MDA-5 is associated with amyopathic myositis and interstitial lung disease and anti-TIF-1γ and anti-NXP-2 with juvenile DM as well as malignancy in patients >40 years. Most MSA have initially been discovered by immunoprecipitation. In routine laboratories, however, MSA are screened for by indirect immunofluorescence and identified by (automated) monospecific immunoassays or by multispecific immunoassays (mainly line/dot immunoassays). Validation of these (multispecific) assays is a challenge as the antibodies are rare and the assays diverse. In this review, we give an overview of the (clinical) performance characteristics of monospecific assays as well as of multispecific assays for detection of MSA. Although most assays are clinically useful, there are differences between techniques and between manufacturers. We discuss that efforts are needed to harmonize and standardize detection of MSA.

Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin-Phosphorylcholine.

Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin-phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1ß, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.