Interleukin-33, endothelin-1, and inflammatory parameters in chronic spontaneous urticaria.

Background: Endothelin-1 (ET-1) and interleukin-33 (IL-33) can modulate the activation of mast cells and basophils in the pathophysiology of allergic diseases, interplaying with other mediators of "low-grade inflammation." Objective: To compare ET-1, IL-33, the neutrophil-lymphocyte ratio (NLR), eosinophil-lymphocyte ratio (ELR), platelet-lymphocyte ratio (PLR), eosinophil-basophil ratio (EBR), systemic immune inflammation index (SII), and system inflammation response index (SIRI) in patients with chronic spontaneous urticaria (CSU) and are antihistamine sensitive (AHS), antihistamine resistant (AHR), omalizumab sensitive (OmS), and omalizumab resistant (OmR). Methods: A prospective observational study enrolled 68 consecutive patients with CSU diagnosed and managed according to the dermatology section of the European Academy of Allergology and Clinical Immunology (EAACI), the European Union funded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization guidelines. Patients with a urticaria control test score of >12 are considered treatment sensitive, and ≤ 12 are considered resistant. The control group consisted of 20 sex-matched subjects without urticarial diseases. Total immunoglobulin E (IgE), antinuclear antibodies (ANA), thyroid stimulating hormone, antithyroid peroxidase, mean platelet volume (MPV), NLR, ELR, PLR, EBR, SII, SIRI, ET-1, and IL-33 were measured at the study entry and compared between the study groups. Results: Thirty AHS group, 38 AHR group, and 20 control group patients were included. The AHS, AHR, and control groups did not differ in demographic parameters, but the CSU groups were characterized by higher indicators of inflammation. In comparison with the AHS group, the AHR group was characterized by higher levels of IL-33 (p = 0.007), ET-1 (p = 0.032), C-reactive protein (p = 0.016), MPV (p = 0.002), and higher rates of positive ANA (p = 0.019). Of the 38 patients from the AHR group, 30 (79%) were included in the OmS group and 8 (21%) were included in the OmR group. The OmR group was characterized by higher levels of C-reactive protein (p = 0.022), EBR (p < 0.001), higher rates of ANA (p = 0.004), and lower levels of ET-1 (p = 0.025) than the OmS group. Conclusion: Our study did not confirm NRL, PRL, SII, and SIRI, PLR as the biomarkers of treatment response to antihistamines and/or omalizumab in CSU. Higher blood levels of IL-33 and ET-1 characterize AHR CSU.

Factors related to omalizumab resistance in chronic spontaneous urticaria.

Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly understood. Objective: To identify clinical and laboratory attributes of patients that may be predictive of OmR in CSU. Methods: We conducted a retrospective observational study by using an electronic patient record data base of patients with severe CSU refractory to a fourfold H1-antihistamine dose, treated with omalizumab 300 mg every 4 weeks for at least 24 weeks. Complete response (CR) was defined as the reduction of baseline urticaria activity score by ≥ 90%, partial response (PR) by ≥ 30% to <90%, and OmR by <30% at 24 weeks. The patient characteristics of the CR, PR, and OmR groups were compared. Results: Sixty-three patients (58.9%) had a complete remission at 24 weeks of omalizumab therapy, and 16 patients (14.9%) had OmR. The patients who were OmR were characterized by a higher rate of arterial hypertension 7 (43.8%), higher mean ± standard deviation (SD) high-sensitivity C-reactive protein (hs-CRP) level (10.3 ± 8.2 mg/L), mean ± SD white blood cell (WBC) count (9.1 ± 2.8 × 10³ cells/mL), and higher mean ± SD C3 level (164.3 ± 45.4 mg/dL) at baseline than the patients with CR (arterial hypertension, 9 [13.1%], p = 0.009; mean ± SD hs-CRP, 3.4 ± 10.1, p = 0.014; mean ± SD WBC count, 6.5 ± 3.8 × 10³ cells/mL, p = 0.012; and mean ± SD C3 level, 121.8 ± 42.1 m/dL, p < 0.001). In multivariable analysis adjusted for age, sex, and body mass index, OmR was associated with an hs-CRP level of >3.0 mg/L (odds ratio 1.94 [95% confidence interval, 1.28-3.15], p = 0.009) and with C3 > 160 mg/dL (odds ratio 1.54 [95% confidence interval, 1.05-2.36], p = .017). Conclusion: Obesity, arterial hypertension, high plasma C3 level, and high-CRP level were associated with OmR in severe CSU.

Association of alopecia areata with atopic dermatitis and chronic spontaneous urticaria.

BACKGROUND: Epidemiologic studies report that alopecia areata (AA) is related to various atopic and autoimmune diseases. The purpose of this study was to identify clinical characteristics and the prevalence of comorbid conditions in Israeli patients with AA. METHODS: This retrospective, matched, case-control study was based on data from an electronic patient record data base. The patients with an electronically documented diagnosis of AA were included in the AA group. The control group was randomly sampled from the remaining subjects, with a case-to-control ratio of two controls for each case. Comorbidity was compared between the study groups. RESULTS: A total of 1751 subjects (49.4% men and 50.6% women), ages 34.9 ± 17.8 years old, were identified. The control group consisted of 3502 age- and sex-matched subjects. The AA group was characterized by a higher blood eosinophil count (0.39 ± 0.12 cells/mm3) than the control group (0.31 ± 0.14 cells/mm3; p < 0.001). In the AA group, there was a higher prevalence of allergic rhinitis (odds ratio [OR] 2.15 [1.85-2.49]; p < 0.001), asthma (OR 1.57 [1.28-1.93]; p < 0.001), atopic dermatitis (AD) (OR 4.17 [3.18-5.47]; p < 0.001), and food allergy (OR 2.79 [1.58-4.91]; p < 0.001) than in the control group. The prevalence of organ-specific and systemic autoimmune diseases was significantly higher in the AA group than in the control group, with the OR of having any autoimmune disease calculated to be 4.72 (3.99-5.57; p < 0.001). The OR of having chronic spontaneous urticaria (CSU) with AA was 6.15 (4.06-9.32; p < 0.001). In patients with concomitant AA and CSU, allergic rhinitis and AD were more prevalent than in patients with CSU in the control group. CONCLUSION: An estimated prevalence of AA among an Israeli population was ∼0.8%. The novel finding of our study was the high prevalence of food allergy and CSU in patients with AA.

Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo.

UNLABELLED: Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (mRNA) expression liver cancer-specific microarray in C/EBPα-saRNA-transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis, and metastasis. Up-regulated genes were enriched for tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation. CONCLUSION: A novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model.

Relationship of Complete Blood Count Derived Biomarkers With Methotrexate Resistance.

Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. Among the therapeutic agents, methotrexate remains a cornerstone of initial treatment. Complete blood count (CBC)-derived biomarkers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic immune response index (SIRI) have been extensively studied in various diseases. Still, their specific role in RA patients undergoing methotrexate treatment has not been investigated. Objective This study aimed to investigate the relationship of CBC-derived biomarkers with methotrexate resistance in newly diagnosed rheumatoid arthritis patients. Methods We performed a comprehensive analysis of 54 RA patients, divided into methotrexate-resistant (MTXR) and methotrexate-sensitive (MTXS) groups. Analysis of variance (ANOVA) was used to assess differences in hematological biomarkers between groups. Standard t-tests were used to compare specific biomarkers between the MTXR and MTXS groups. The chi-squared test was used to compare categorical variables between groups. Pearson's correlation test was also used to examine correlations between these biomarkers and Disease Activity Score 28 (DAS28) in both groups. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker to determine predictive ability. Results A statistically increased PLR ratio was observed in the MTXR group compared to the MTXS group. Significant correlations between DAS28 and NLR, PLR, SII, and SIRI were observed in the MTXR group. In contrast, these correlations were absent in the MTXS group. In addition to PLR, DAS28 and ESR were significantly higher in the MTXR group than in the MTXS group. None of these biomarkers showed prognostic value for methotrexate treatment outcomes. Conclusion PLR could be used as a biomarker for resistance to methotrexate treatment in a specific RA patient population. Increased PLR and ESR, together with higher DAS28, might be associated with a more pronounced inflammatory state in MTXR patients.

A case of improved quality of life in a patient with inoperable pancreatic cancer after repeated RFA.

Radiofrequency ablation (RFA) has widespread popularity due to its immune-modulation effects in many cancers. Optimal settings to apply RFA in pancreatic cancer, in which the advanced stage of the tumor at the diagnosis makes various therapeutic approaches fail, are still demanding. We report the case of a patient with unresectable pancreatic cancer in which 3 repetitive RFA has been applied over a period of 3 months. Results revealed an improvement in the patient's clinical condition associated with the reduced incidence of CD4+CD45RO+ T lymphocytes and declined TGF-ß level in serum. The good quality of life and disease-free survival were maintained for the next months. Booster application of RFA procedure might be a promising option to improve the quality of life in pancreatic cancer patients.

Harmonizing allergy care-integrated care pathways and multidisciplinary approaches.

There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the "second translational gap". A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care. We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidelines provide the core knowledge, the key component of implementation involves education, training, and support of all healthcare professionals (HCPs), patients and their caregivers. The pathways should define the level of competence required for each clinical task. It may be useful to leave the setting of care delivery or the specific HCP involved undefined to account for variable patterns of health service delivery as well as local socioeconomic, ethnic, environmental, and political imperatives. In all cases, where competence is exceeded, it is necessary to refer to the next stage in the pathway. The success and sustainability of ICPs would ideally be judged by patient experience, health outcomes, and health economics. We provide examples of successful programs, most notably from Finland, but recommend that further research is required in diverse settings to optimize outcomes worldwide.

Allergy education and training for physicians.

The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of "allergy" as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence  to manage  mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly. In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care. We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide.

Recurrent spontaneous clearance of psoriasis during exacerbations of concomitant chronic spontaneous urticaria.

In this case report, we describe a patient with a chronological relationship between exacerbations of chronic spontaneous urticaria and remissions of concomitant generalized plaque psoriasis.

Cured giant hepatocellular carcinoma after transarterial embolization complicated with liver abscess formation.

Many patients with hepatocellular carcinoma cannot be treated surgically because of the advanced stage of the tumor and/or coexisting cirrhosis. Transcatheter arterial embolization (TAE) represents an alternative therapeutic approach for some of these patients. However, it is not a curative measure, and an additional therapy is required to eradicate the residual disease. In this communication, we report a case of 55-year-old man with giant hepatocellular carcinoma located in the right lobe of the liver that was successfully treated with TAE. TAE completely devascularized the tumor in one session. Despite of postembolization antibiotic therapy, complete tumor necrosis led to abscess formation. After 57 days of abscess drainage, necrotic tumor tissue was completely evacuated from the drained cavity; no viable tumor tissue was identified by computed tomography/magnetic resonance imaging scan on a 5 year follow-up. TAE procedure can be suggested as a modulator of antitumor immune response, by exposing tumor antigens after necrosis leading to inflammation. In addition to necrosis caused by TAE, an antimicrobial acute inflammatory reaction in the treated area led to the complete destruction of the giant tumor.

Immunomodulatory Changes Following Isolated RF Ablation in Colorectal Liver Metastases: A Case Report.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in developed countries. The liver is the most prevalent site of metastasis from CRC. Currently, the gold-standard treatment for colorectal liver metastases (CLMs) is surgical resection. However, depending on the pattern of the disease, a significant number of patients may require different approaches alone or in combination with surgery, including thermal ablation (radiofrequency (RFA) or microwave (MWA) ablation) or transarterial liver-directed therapies, although the latter is not yet part of the standard treatment for CRC liver metastases. Methods and Results: We present the case of a 63-yearold man with bilobar CLM who was treated with transarterial embolization (TAE) and RFA followed by chemotherapy. A post-RFA study of immune parameters revealed the downregulation of CD39 expression in the circulating CD4+ T cell population and a reduction of the serum levels of cytokines IL-10, TGF-ß, IFN-gamma and IL-17, which positively correlated with the diminished serum level of gamma-glutamyl transferase (GGT) and the subdued inflammatory markers: the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). Later, the patient underwent chemotherapy. Liver failure developed within two years and nine months following tumour ablation, leading to the death of the patient. Conclusions: However, the denial of adjuvant chemotherapy by the patient gave us the opportunity to assess the immunomodulatory changes following RFA in the absence of any other therapeutic modalities.

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis.

Guillain-Barré syndrome (GBS) is an immune-mediated acute disorder of the peripheral nervous system. Despite treatment, there is an associated mortality and severe disability in 9 to 17% of the cases. Decitabine (DAC) is a hypomethylating drug used in myelodisplastic syndrome, that has been shown to exert immunomodulatory effects. We have evaluated the effects of DAC in two rodent models of GBS, the Experimental Allergic Neuritis (EAN). Both prophylactic and therapeutic treatment with DAC ameliorated the clinical course of EAN, increasing the numbers of thymic regulatory T cells and reducing the production of proinflammmatory cytokines. Our data suggest the possible use of decitabine for the treatment of GBS.

Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer.

Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes. Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate. Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38). Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings.

Long-term survival in a patient with low-level inflammatory markers and liver metastasis, converted resectable by TACE.

Case report presents the successful treatment of unresectable liver metastasis in a patient with colon cancer. A 44-year-old male underwent right hemicolectomy followed by capecitabine for a moderately differentiated adenocarcinoma of the colon. 2 years later, a liver metastatic lesion was detected and had increased in size despite chemotherapy with capecitabine plus oxaliplatin (XELOX). Curative liver resection was conducted after conversion of unresectable tumor to resectable by transarterial chemoembolization followed by chemotherapy - irinotecan with fluorouracil and folinic acid (FOLFIRI). No recurrence was observed during 22-month follow-up after hepatectomy.

Possible therapeutic role of IgE blockade in irritable bowel syndrome.

Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I IgE Fc receptors on mast cells (MCs) and basophils, inhibiting the IgE immune pathway. Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain. Pharmacologic control of MC activation and mediator release is a current area of active interest in the field of IBS research. Recently, we and Pearson et al described 2 cases of patients with IBS with diarrhea (IBS-D) showing positive clinical response to omalizumab. In both cases, the female patients had severe, long-lasting IBS-D and achieved an almost complete resolution of IBS symptoms. Both patients were also able to discontinue all IBS medications after commencing the anti-IgE therapy. For both patients, the omalizumab treatment showed a relatively rapid onset of action, resembling the efficacy observed in and previously reported for patients with chronic spontaneous urticaria. In this Editorial, we discuss the possible biological mechanisms that may underlie the clinical efficacy of omalizumab in IBS. We suggest that there is a need for a well-designed prospective study to investigate the therapeutic effects of anti-IgE in IBS.

Tumor Regression in HCC Patient with Portal Vein Tumor Thrombosis after Intraportal Radiofrequency Thermal Ablation.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Portal vein tumor thrombosis (PVTT) is a frequent entity in HCC, which strictly limits the gold standard treatment options such as surgical resection and transarterial chemoembolization. Therefore, the prognosis of patients with PVTT is extremely poor and an emergence of seeking an alternative option for intervention is inevitable. We present a case of a 60-year-old male patient with HCC induced PVTT who was subjected to the intraportal RFA and stenting-VesOpen procedure. No additional medical intervention was performed. The repeated CT performed 5 months after the VesOpen procedure revealed significant decrease of the tumor size, patent right, and main portal vein and a recanalization of the left portal vein, which was not processed. At this time point, liver functional tests, appetite, and general condition of the patient were improved evidently. This report designates the RFA as an instrumental option of therapeutic intervention for HCC patients with PVTT.

The effect of citrus peel extracts on cytokines levels and T regulatory cells in acute liver injury.

BACKGROUND: T cell-mediated immune responses contribute to the hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of antioxidant, anti-inflammatory mixture of citrus peel extract (CPE) on the immune-mediated liver injury. METHODS: The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring frequency of T regulatory cells (Tregs), cytokines (TNF-α, IL-10, and IFN-γ), and nitric oxide levels. RESULTS: The CPE application notably prevents development of liver injury through decreasing levels of both cytokines (TNF-alpha, INF) and regulatory T cells and increasing levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in evident reduction of the liver damage. CONCLUSION: Our findings represent the primary preclinical data indicating that the CPE in vivo could ameliorate Con A induced hepatitis. The low dose of CPE most likely can be used for the treatment of the T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis.

Heme oxygenase-1 expression in peripheral blood mononuclear cells correlates with disease activity in multiple sclerosis.

Multiple sclerosis (MS) is an immunoinflammatory disease that affects the central nervous system. Heme oxygenase-1 (HO-1) is one of the three isoforms of the heme oxygenase enzyme that catabolyzes the degradation of heme into biliverdin with the production of free iron and CO. We show in this study that HO-1 expression is reduced in PBMCs of MS patients and that during exacerbation of the disease there is a significant downregulation of this enzyme. We conclude that HO-1 may play a significant role in the maintenance of immune homeostasis which is disrupted in autoimmune disorders, such as MS.