Use Of Immune Modulators Research Articles

The Role of Dicrocoelium dendriticum Egg Antigen in Colitis: A Molecular, Pathological and Serological Study in an Experimental Model of C57BL/6 Mice.

Inflammatory bowel disease (IBD) is a chronic and recurrent disease of the gastrointestinal tract that enhances the chance of developing colorectal cancer. Since standard treatments such as Mesalazine have limited effectiveness and are often accompanied by numerous side effects, the use of immune modulators derived from worms has been proposed as a new immunotherapy method for inflammatory diseases such as ulcerative colitis. The aim of this study is to investigate the protective effects of D. dendriticum egg antigen on DSS-induced colitis in C57BL/6 mice. D. dendriticum egg antigen was extracted and DSS (3.5%) was used to induce colitis in mice. Treatment and prophylaxis included intraperitoneal injections of D. dendriticum egg antigen. Histopathological indicators and the disease activity index (DAI), including weight loss, rectal bleeding, stool consistency, and rectal prolapse, were used to assess the severity of colitis. Real-time PCR measured the expression of transforming growth factor-β (TGF-β) and interleukin-17 (IL-17), while ELISA determined the concentration of these cytokines. Treatment with D. dendriticum egg antigen significantly improved the clinical symptoms and decreased the severity of DSS-induced colitis. Furthermore, D. dendriticum egg antigen increased the expression of TGF-β mRNA and reduced the expression of IL-17 mRNA, leading to a positive adjustment in the regulation of proteins and reduction of inflammatory proteins. As a result, the macroscopic, microscopic inflammation and activity index (DAI) of DSS-induced decreased. D. dendriticum egg antigen provides a promising new way to modulate the immune system and improve ulcerative colitis.

Overview of dendritic cells and related pathways in autoimmune uveitis.

Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immune responses. They are widely distributed in various tissues and organs, including the eyes. In the ocular context, permanent DCs are present at the peripheral edge of the retina and the peripapillary area in an immature state. However, during the inflammatory process, DCs become activated and contribute to the development of uveitis. This review focuses on introducing the characteristics and status of DC-induced uveitis, exploring factors that can influence the status of DCs, and discussing feasible methods for treating DCs in both experimental autoimmune uveitis animal models and humans. It emphasizes the importance of further research on molecular pathways and signaling pathways that regulate the function of DCs. For example, investigating molecules such as cytotoxic T-lymphocyte-associated protein 4, which inhibits the B7-CD28 co-stimulatory interaction, can help improve immune homeostasis. The aim is to identify new therapeutic targets and develop targeted strategies for DCs, such as DC vaccine therapy or the use of immune modulators. These approaches can be tailored to the immune characteristics and disease manifestations of individual patients, enabling personalized treatment strategies. This may include the personalized design and precise medication of DC therapy, with the ultimate goal of improving treatment efficacy while minimizing adverse reactions.

Flt3 agonist enhances immunogenicity of arenavirus vector-based simian immunodeficiency virus vaccine in macaques.

Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens are capable of inducing efficacious humoral and cellular immune responses in nonhuman primates. Several studies have evaluated the use of immune modulators to further enhance vaccine-induced T-cell responses. The hematopoietic growth factor Flt3L drives the expansion of various bone marrow progenitor populations, and administration of Flt3L was shown to promote expansion of dendritic cell populations in spleen and blood, which are targets of arenaviral vectors. Therefore, we evaluated the potential of Flt3 signaling to enhance the immunogenicity of arenaviral vaccines encoding SIV immunogens (SIVSME543 Gag, Env, and Pol) in rhesus macaques, with a rhesus-specific engineered Flt3L-Fc fusion protein. In healthy animals, administration of Flt3L-Fc led to a 10- to 100-fold increase in type 1 dendritic cells 7 days after dosing, with no antidrug antibody (ADA) generation after repeated dosing. We observed that administration of Flt3L-Fc fusion protein 7 days before arenaviral vaccine increased the frequency and activation of innate immune cells and enhanced T-cell activation with no treatment-related adverse events. Flt3L-Fc administration induced early innate immune activation, leading to a significant enhancement in magnitude, breadth, and polyfunctionality of vaccine-induced T-cell responses. The Flt3L-Fc enhancement in vaccine immunogenicity was comparable to a combination with αCTLA-4 and supports the use of safe and effective variants of Flt3L to augment therapeutic vaccine-induced T-cell responses.IMPORTANCEInduction of a robust human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell response through therapeutic vaccination is considered essential for HIV cure. Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens have demonstrated strong immunogenicity and efficacy in nonhuman primates. Here, we demonstrate that the immunogenicity of arenaviral vectors encoding SIV immunogens can be enhanced by administration of Flt3L-Fc fusion protein 7 days before vaccination. Flt3L-Fc-mediated increase in dendritic cells led to robust improvements in vaccine-induced T- and B-cell responses compared with vaccine alone, and Flt3L-Fc dosing was not associated with any treatment-related adverse events. Importantly, immune modulation by either Flt3L-Fc or αCTLA-4 led to comparable enhancement in vaccine response. These results indicate that the addition of Flt3L-Fc fusion protein before vaccine administration can significantly enhance vaccine immunogenicity. Thus, safe and effective Flt3L variants could be utilized as part of a combination therapy for HIV cure.

Surgical Management of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory disease of the skin, characterized by recurrent draining sinuses and abscesses, predominantly in skin folds carrying terminal hairs and apocrine glands. Treatment for this debilitating disease has been medical management with antibiotics and immune modulators. With the advent of better reconstructive surgical techniques, the role of surgery in the treatment of HS has expanded, from being a last resort to a modality that is deployed earlier. Larger defects can be more easily reconstructed, allowing for a more radical excision of diseased areas. Locoregional flaps, perforator flaps, and propeller flaps that use the fasciocutaneous tissue allow reconstruction of defects with similar tissue, and provide better cosmetic and functional outcomes. They are easy to execute and can be performed even in resource-poor settings with concurrent use of immune modulators and postoperative antibiotics. Hidradenitis can be successfully treated with surgery in early stages as well as severe disease, due to the advances in understanding disease behavior, multidisciplinary care, and advanced reconstructive techniques. Coupled with a multidisciplinary care team, surgery offers a durable, lasting cure for HS, significantly reducing disease morbidity.

Helminth Lessons in Inflammatory Bowel Diseases (IBD).

Helminths are multicellular invertebrates that colonize the gut of many vertebrate animals including humans. This colonization can result in pathology, which requires treatment. It can also lead to a commensal and possibly even a symbiotic relationship where the helminth and the host benefit from each other's presence. Epidemiological data have linked helminth exposure to protection from immune disorders that include a wide range of diseases, such as allergies, autoimmune illnesses, and idiopathic inflammatory disorders of the gut, which are grouped as inflammatory bowel diseases (IBD). Treatment of moderate to severe IBD involves the use of immune modulators and biologics, which can cause life-threatening complications. In this setting, their safety profile makes helminths or helminth products attractive as novel therapeutic approaches to treat IBD or other immune disorders. Helminths stimulate T helper-2 (Th2) and immune regulatory pathways, which are targeted in IBD treatment. Epidemiological explorations, basic science studies, and clinical research on helminths can lead to the development of safe, potent, and novel therapeutic approaches to prevent or treat IBD in addition to other immune disorders.

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19.

Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response. We prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively. A total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group. There were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.

Murine glial progenitor cells transplantation and synthetic PreImplantation Factor (sPIF) reduces inflammation and early motor impairment in ALS mice

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuronal disorder characterized by neuronal degeneration and currently no effective cure is available to stop or delay the disease from progression. Transplantation of murine glial-restricted precursors (mGRPs) is an attractive strategy to modulate ALS development and advancements such as the use of immune modulators could potentially extend graft survival and function. Using a well-established ALS transgenic mouse model (SOD1G93A), we tested mGRPs in combination with the immune modulators synthetic PreImplantation Factor (sPIF), Tacrolimus (Tac), and Costimulatory Blockade (CB). We report that transplantation of mGRPs into the cisterna magna did not result in increased mice survival. The addition of immunomodulatory regimes again did not increase mice lifespan but improved motor functions and sPIF was superior compared to other immune modulators. Immune modulators did not affect mGRPs engraftment significantly but reduced pro-inflammatory cytokine production. Finally, sPIF and CB reduced the number of microglial cells and prevented neuronal number loss. Given the safety profile and a neuroprotective potential of sPIF, we envision its clinical application in near future.

Future of Therapy for Inborn Errors of Immunity.

Over the past 20 years, the rapid evolution in the diagnosis and treatment of primary immunodeficiencies (PI) and the recognition of immune dysregulation as a feature in some have prompted the use of “inborn errors of immunity” (IEI) as a more encompassing term used to describe these disorders [1, 2] . This article aims to review the future of therapy of PI/IEI (referred to IEI throughout this paper). Historically, immune deficiencies have been characterized as monogenic disorders resulting in immune deficiencies affecting T cells, B cells, combination of T and B cells, or innate immune disorders. More recently, immunologists are also recognizing a variety of phenotypes associated with one genotype or similar phenotypes across genotypes and a role for incomplete penetrance or variable expressivity of some genes causing inborn errors of immunity [3]. The IUIS classification of immune deficiencies (IEIs) has evolved over time to include 10 categories, with disorders of immune dysregulation accounting for a new subset, some treatable with small molecule inhibitors or biologics. [1] Until recently, management options were limited to prompt treatment of infections, gammaglobulin replacement, and possibly bone marrow transplant depending on the defect. Available therapies have expanded to include small molecule inhibitors, biologics, gene therapy, and the use of adoptive transfer of virus-specific T cells to fight viral infections in immunocompromised patients. Several significant contributions to the field of clinical immunology have fueled the rapid advancement of therapies over the past two decades. Among these are educational efforts to recruit young immunologists to the field resulting in the growth of a world-wide community of clinicians and investigators interested in rare diseases, efforts to increase awareness of IEI globally contributing to international collaborations, along with advancements in diagnostic genetic testing, newborn screening, molecular biology techniques, gene correction, use of immune modulators, and ex vivo expansion of engineered T cells for therapeutic use. The development and widespread use of newborn screening have helped to identify severe combined immune deficiency (SCID) earlier resulting in better outcomes [4]. Continual improvements and accessibility of genetic sequencing have helped to identify new IEI diseases at an accelerated pace [5]. Advances in gene therapy and bone marrow transplant have made treatments possible in otherwise fatal diseases. Furthermore, the increased awareness of IEI across the world has driven networks of immunologists working together to improve the diagnosis and treatment of these rare diseases. These improvements in the diagnosis and treatment of IEI noted over the past 20 years bring hope for a better future for the IEI community. This paper will review future directions in a few of the newer therapies emerging for IEI. For easy reference, most of the diseases discussed in this paper are briefly described in a summary table, in the order mentioned within the paper (Appendix).

Staging Pouch Surgery in Ulcerative Colitis in the Biological Era.

Restorative proctocolectomy, or ileal pouch anal anastomosis, is considered the standard treatment for intractable ulcerative colitis. When the pelvic pouch was first introduced in 1978, a two-stage procedure with proctocolectomy, construction of the pelvic pouch, and a diverting loop with subsequent closure were suggested. Over the decades that the pelvic pouch has been around, some principal technical issues have been addressed to improve the method. In more recent days the laparoscopic approach has been additionally introduced. During the same time-period the medical arsenal has developed far more with the increasing use of immune modulators and the introduction of biologicals. Staging of restorative proctocolectomy with a pelvic pouch refers to how many sessions, or stages, the procedure should be divided into. The main goal with restorative proctocolectomy is a safe operation with optimal short- and long-term function. In this paper we aim to review the present knowledge and views on staging of the pouch procedure in ulcerative colitis, especially with consideration to the treatment with biologicals.

Immune-Modulators and Thyroid Function in Oncological Patients with Hashimoto 'S Thyroiditis

Hashimoto's thyroiditis (HT) is a form of chronic lymphocytic thyoriditis, of autoimmune origin and multiple physiopathogenic pathways, which may or may not be associated with other autoantibody diseases, both endocrinological (P.A.S.) and non-endocrinological (M.A.S.). Likewise, HT can coincide -in the same patient- with very varied oncological pathologies, with which it can interact in a usually negative way. In this article, the benefit achieved in cancer patients who also had HT is evaluated through the use of immune-modulators.

Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents.

Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most Mycobacterium tuberculosis (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb’s differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs de-novo is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host’s antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents.

Weighing the benefits and risks of oral immunotherapy in clinical practice

Food allergies are common and affect 6-8% of children in the United States; they pose a significant burden on the quality of life of children with allergy and their caregivers due to multiple daily restrictions. Despite the recommended dietary avoidance, reactions tend to occur due to unintentional exposure to the allergenic food trigger. Fear of accidental ingestions with potentially severe reactions, including anaphylaxis and death, creates anxiety in individuals with food allergy. Oral immunotherapy has emerged as a form of active and potentially disease-modifying treatment for common food allergies encountered in childhood. The efficacy of oral immunotherapy is high, with the majority of participants achieving desensitization and, as a result, protection from trace exposures and improved quality of life. The main risk of oral immunotherapy consists of allergic reactions to treatment. In general, rates of allergic reactions and anaphylaxis are reported to be higher in individuals pursuing therapy options, but most subjects who undergo oral immunotherapy will likely experience mild or moderate reactions during treatment. Adverse events tend to reduce in both frequency and number in the maintenance period. The use of immune modulators alongside oral immunotherapy has been suggested, with the aim to improve efficacy and safety, and to facilitate the overall process. It is evident that the landscape of food allergy management is changing and that the future looks brighter, with different options emerging over time. The process of how to choose the appropriate option becomes a discussion between the clinician and the patient, which involves a joint review of the current medical evidence but also the patient's preference for balancing particular attributes of the treatment. By working together, providers and patients will ensure achievement of the best possible outcome for children with food allergies.

Abstract P512: Immune Correlates of Functional Outcome in Acute Ischemic Stroke (AIS) Patients

Introduction: Acute Ischemic Stroke (AIS) is one of the leading causes of disability and death in US. Although Endovascular Therapy (EVT) remains the mainstay therapy during acute phase for large vessel occlusions (LVOs), functional outcome varies among the treated patients. This ischemic injury results in an inflammatory response which plays an important role in the functional and neurological outcomes. We hypothesize that the early changes in the inflammatory response near the site of occlusion can be used as predictor of long-term neurofunctional decline Methods: AIS-LVO patients presenting to an academic comprehensive stroke center (CSC) within 24 hours from their last known well and undergoing EVT were included. Blood was collected proximal and distal to the thrombus during thrombectomy. Control samples were collected from the femoral artery and median cubital vein. Cytokine analysis and deep immune profiling was performed using a 20-parameter bead array and 13-parameter flow cytometer. Least Absolute Shrinkage and Selection Operator (LASSO) models were used for cell selection and correlation was evaluated for outcomes including mRS, NIHSS, MOCA and mortality, using R-software. Results: With 19 patients meeting the inclusion criteria, cytokine analysis revealed a significant increase in MMP and IFN-g, and decrease in GM-CSF, IL17, TNF-α, IL6, MIP-1a, and MIP-1b distal to clot. Flow cytometry analysis revealed a significant decrease in NK-T-cells, and CD8 T-cells counts and a relative increase in GM-CSF+ and IL17+ CD4 T-cells distal to clot. Immunological and neurological analysis revealed a correlation with CD4 + IFN-γ - IL10 + (r=0.7) & CD8 + IFN-γ - GMCSF + (0.6) with mRS, and CD4 + IFN-γ - IL10 + (r=0.7), CD4+ IFN-γ - IL17 + (r= -0.6), & CD8 + IFN-γ + IL17 + (r=0.7) cells with mortality. Conclusion: Our results indicate that local ischemia results in a hyperacute adaptive immune response at the site of occlusion. This immune response is predictive of functional outcome among AIS patients and is impactful in multiple ways, including the use of supportive therapy for patients with a poor functional trajectory and the use of immune-modulators at the site of ischemic injury.

Prognostic relevance of lymphocytopenia, monocytopenia and lymphocyte-to-monocyte ratio in primary myelodysplastic syndromes: a single center experience in 889 patients

Current prognostic models for myelodysplastic syndromes (MDS), including the Revised International Prognostic Scoring System (IPSS-R), do not account for host immunity. We retrospectively examined the prognostic relevance of monocytopenia, lymphocytopenia and lymphocyte-to-monocyte ratio (LMR) in a cohort of 889 patients with primary MDS. After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformation were documented. In univariate analysis, subnormal absolute lymphocyte count (ALC) <0.9 × 109/l; P=0.001), ALC<1.2 × 109/l (P=0.0002), subnormal absolute monocyte count (AMC) <0.3 × 109/l (P=0.0003), LMR (P⩽0.0001) and LMR⩾5 (P=0.03) were all associated with inferior overall survival. In multivariable analysis that included other risk factors, significance was retained for LMR (P=0.02) and became borderline for ALC <1.2 × 109/l (P=0.06). Analysis in the context of IPSS-R resulted in P-values of 0.06 for ALC<1.2 × 109/l, 0.7 for monocytopenia and 0.2 for LMR. Leukemia-free survival was not affected by ALC, AMC or LMR. The observations from the current study suggest a possible detrimental role for altered host immunity in primary MDS, which might partly explain the therapeutic benefit of immune-directed therapy, including the use of immune modulators; however, IPSS-R-independent prognostic value for either ALC or AMC was limited.

Association of Mean Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Prospective Study: ACG Fellow Award

Introduction: Emerging data suggests that vitamin D deficiency is implicated in the pathogenesis and disease activity of inflammatory bowel diseases (IBD). We sought to determine the relationship between mean vitamin D status over a multiyear time period with clinical course in IBD patients. Methods: We used a prospective, longitudinal IBD natural history registry, focusing on patients with 5 years of follow-up. Mean vitamin D levels <30 ng/mL were defined as low and higher mean levels were considered normal. IBD clinical status was approximated with patterns of medication use (steroids, immune-modulators, biologics, and narcotics), healthcare utilization (phone calls, emergency department (ED) visit, clinic visits, CT scans, hospital admissions, and surgery), bio-markers (erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP) levels), disease activity scores (Harvey-Bradshaw index, ulcerative colitis (UC) disease activity index) and health related quality of life (SIBDQ). Results: Nine hundred forty-four IBD patients formed the study population (mean age 44 years; 52.3% female). Of the patients 30.1% had low mean vitamin D levels. The mean number of vitamin D tests was 3.4 per subject. Over the 5 year study period, IBD patients with low vitamin D levels required significantly more steroids, biologics, narcotics, CT scans, ED visits, hospitalizations, and surgery compared to those with normal mean vitamin D levels. Moreover, subjects with low vitamin D had more abdominal pain, worse disease activity, and poorer quality of life (Table 1). There was no difference in patterns of CRP & ESR levels, frequency of phone calls or clinic visits, and use of immune-modulators between the two groups.Table 1: IBD Disease Activity IndicatorsConclusion: In IBD patients, low mean vitamin D levels are associated with worse disease activity and higher morbidity including increased pain, higher healthcare utilization, and increased need for medications. Future studies that explore the potential mechanism(s) by which vitamin D modulates IBD activity are warranted.

Considerations in the design of clinical trials for multibacillary leprosy treatment

In 1991, the World Health Assembly adopted a resolution to attain the goal of global elimination of leprosy as a public health problem by the year 2000, based on universal access to multidrug therapy established by the WHO. The WHO multidrug therapy recommendation was not based on clinical trial results, but was based on all scientific knowledge available at the time and incorporated some financial constraints, such as the impossibility of daily rifampin use. Further decisions regarding treatment duration were needed to allow the World Health Assembly resolution target to be reached, which was set without a deep epidemiological evaluation. At present there are many uncertainties about leprosy treatment, including for instance, its ideal duration including decisions concerning daily or intermittent use of drugs, the use of immune modulators with antibacterial drugs as prophylaxis, and treatment of reactions during and after chemotherapy. To advance our knowledge of leprosy treatment, knowledge revision of the available research would be the first step to develop comprehensive Bayesian clinical trials designed to shed light on these uncertainties.

Inflammation Is an Independent Risk Factor for Colonic Neoplasia in Patients With Ulcerative Colitis: A Case–Control Study

An association between inflammatory activity and colorectal neoplasia (CRN) has been documented in patients with ulcerative colitis (UC). However, previous studies did not address the duration of inflammation or the effects of therapy on risk for CRN. We investigated the effects of inflammation, therapies, and characteristics of patients with UC on their risk for CRN. We collected data from 141 patients with UC without CRN (controls) and 59 matched patients with UC who developed CRN (cases), comparing disease extent and duration and patients' ages. We used a new 6-point histologic inflammatory activity (HIA) scale to score biopsy fragments (n = 4449). Information on medications, smoking status, primary sclerosing cholangitis, and family history of CRN were collected from the University of Chicago Inflammatory Bowel Disease Endoscopy Database. Relationships between HIA, clinical features, and CRN were assessed by conditional logistic regression. Cases and controls were similar in numbers of procedures and biopsies, exposure to steroids or mesalamine, smoking status, and family history of CRN. They differed in proportion of men vs women, exposure to immune modulators, and primary sclerosing cholangitis prevalence. In univariate analysis, HIA was positively associated with CRN (odds ratio [OR], 2.56 per unit increase; P = .001), whereas immune modulators (including azathioprine, 6-mercaptopurine, and methotrexate) reduced the risk for CRN (OR, 0.35; P < .01). HIA was also associated with CRN in multivariate analysis (OR, 3.68; P = .001). In a case-control study, we associated increased inflammation with CRN in patients with UC. Use of immune modulators reduced the risk for CRN, indicating that these drugs have chemoprotective effects. On the basis of these data, we propose new stratified surveillance and treatment strategies to prevent and detect CRN in patients with UC.

Prevalence and clinical significance of anti-C1q antibodies in cutaneous and systemic lupus erythematosus

Autoantibodies against C1q are strongly linked to immune-complex disorders like systemic lupus erythematosus (SLE). Although anti-C1q antibodies have received much interest in the recent years, their biological functions remain unclear. Anti-C1q antibodies are strongly associated with lupus nephritis. The aim of this study was to determine the prevalence of anti-C1q antibodies in Egyptian lupus patients as well as to evaluate the associations between anti C1q antibodies and clinical and serologic parameters of patients with cutaneous and systemic lupus erythematosus.Fifty-eight patients of lupus erythematosus were recruited in the study, and they were divided into 3 groups according to their clinical presentations and laboratory investigations; group (1) consists of 20 patients with musculoskeletal manifestations, mainly arthritis (34.5%), group (2) consists of 12 patients with lupus nephritis (20%), and group (3) consists of 26 patients with cutaneous lupus (44.8%). Fourteen age and sex matched healthy subjects served as controls. Complete blood picture, kidney function tests, liver function tests and anti-double stranded DNA were done for all the studied patients. Anti-C1q antibodies were determined by immunometric enzyme immunoassay for all the studied subjects.Anti-C1q antibodies were positive in (63.8%) of lupus erythematosus (LE) patients and (0%) of controls. Moreover, the serum anti-C1q antibodies titers were significantly higher (P<0.001) in all lupus erythematosus patients (both systemic and cutaneous) when compared to healthy controls. Surprisingly, serum anti-C1q antibodies were significantly higher in patients with cutaneous lupus than those with lupus nephritis (P<0.001). Anti-C1q titers were significantly correlated with levels of anti–double stranded DNA (P<0.001), as well as with proteinuria (<0.05) in lupus nephritis patients.It was concluded that anti C1q antibodies might play a pathogenic role in the pathogenesis of cutaneous lupus and could positively be associated with evolution to SLE. Moreover, it could predict patients who subsequently develop nephritis, thus early use of immune modulators in cutaneous lupus could improve patients’ prognosis by decreasing the possibility of evolution to systemic lupus complications, mainly nephritis.

Tu1293 Increasing Hospitalization and Decreasing in-Hospital Mortality Related to Crohn's Disease in the United States

Background and Aims: The incidence of Crohn's Disease (CD) in certain regions has been reported to be stable over the past 20-30 years. The prevalence of CD is as high as 630,000 persons in North America. Despite a stable incidence, prevalence continues to rise thus increasing the healthcare burden. Direct medical costs for CD have been estimated at 7.811.2 billion per year in the United States, about 31-57% of which is from inpatient stays. The aim of this study was to determine trends in hospitalization rates and in-hospital mortality for patients with Crohn's disease. Methods: This was a retrospective cohort study. The Nationwide Inpatient Sample database was utilized for inpatient data analysis from 1988-2006. Patients with primary diagnosis of Crohn's disease ICD-9-CM discharge diagnose (555.0, 555.1 ,555.2 and 555.9) were included . ANOVA was used to evaluate trends, and Linear Poisson multivariate regression model was used to control for variations in age, gender, time of diagnosis and ethnicity. Results: Age adjusted rates of Hospitalizations for CD increased 25% from 166 per 100,000 persons in 1993 to 208 per 100,000 persons in 2006 (p<0.01). Overall, there has been a 12% increase in hospitalizations since 1988 (p<0.01). The mean age of admission was 62, 55% white, 8% black, and 5% Hispanic. During this period, there were 239,159 deaths with a mean age of 72. 47% were male and 53% were female. 56% were white, 8% were black and 5% were Hispanics. Age adjusted rates of mortality have declined significantly from 494 per 100,000 persons in 1988 to 313 per 100,000 persons in 2006 (p<0.01). There has been a decline in mortality rate of 36% since 1988 and a decline of 22% since 1999 (p<0.01). Conclusions: The hospitalization rate of Crohn's disease has been increasing over the last two decades. Mortality has decreased by 36 per cent in this time period and may be related to the widespread use of immune modulators and biologics.

Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: A need for early immune-modulators for severe cases

SummaryIt has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of ‘protein homeostasis system’; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune-modulators with antiviral agents for severe pneumonia patients may reduce morbidity and prevent progressive fatal pneumonia.