Systemic Immunological Diseases Research Articles

Fifty Years of Handedness Research: A Neurological and Methodological Update.

Handedness, a complex human aspect that reflects the functional lateralization of the hemispheres, also interacts with the immune system. This study aimed to expand the knowledge of the lateralization of hand, foot, and eye activities in patients with immune-mediated (IM) or other (noIM) neurological diseases and to clarify the properties of the Edinburgh Handedness Inventory (EHI) in an Italian population. Three hundred thirty-four patients with IM or noIM diseases affecting the brain or spine and peripheral nervous system were interviewed about stressful events preceding the disease, subjective handedness, and familiarity for left-handedness or ambidexterity. The patients and 40 healthy subjects underwent EHI examination. In the whole group of participants, 24 items of the EHI were classified into five factors (Hand Transitive, Hand Refined, Hand Median, Foot, Eye), demonstrating good reliability and validity. Chronological age had a significant influence on hand and foot EHI factors and the laterality quotient (LQ), particularly on writing and painting. In the patient groups, EHI factors and the LQ were also predicted by age of disease onset, duration of disease, and family history of left-handedness or ambidexterity. No differences were found between patients and healthy subjects, but pencil use scored significantly lower in patients with IM diseases than in those with noIM brain diseases. These results demonstrate that the lateralization of hand and foot activities is not a fixed human aspect, but that it can change throughout life, especially for abstract and symbolic activities. Chronic neurological diseases can cause changes in handedness. This may explain why, unlike systemic immunological diseases, IM neurological diseases are not closely associated with left-handedness. In these patients, the long version of the EHI is appropriate for determining the lateralization of body activities to contextualize the neurological picture; therefore, these findings extend the Italian normative data sets.

Mortality and Comorbidities of Covid-19 Patients with Immune Thrombocytopenic Purpura - a Review of the National Database 2019-2020

Introduction: Immune thrombocytopenic purpura (ITP) is a diagnosis of exclusion that is characterized by isolated thrombocytopenia with a generalized purpuric rash. If there is a known case for the ITP, it is referred to as secondary ITP. Secondary ITP may often be caused by drugs, systemic immunologic, or infectious diseases. Covid-19 is a disease caused by the SARS-CoV-2 virus, which caused a pandemic in 2020, affecting hundreds of millions of people worldwide. There have been several different hematologic conditions associated with this viral infection, including deep vein thromboses, pulmonary emboli, and many patients with ITP induced by Covid-19. With several case reports and case series available on these patients, the specifics behind the strength of the association, mortality of the patients, and their comorbidities have not been previously explored. Methods: Using the national inpatient sample from the years 2019-2020, we analyzed adult hospitalized patients with ITP and Covid-19 based on their International Classification of Diseases - 10 clinical modification codes. We calculated the odds ratios for patients with Covid-19 being diagnosed with ITP compared to other hospitalized patients. Additionally, we calculated the odds of several complications, treatments, as well as concurrent conditions in patients with Covid-19 and ITP. The complications measured were epistaxis or hemoptysis, intracranial hemorrhage (ICH), non-intracranial hemorrhage (nICH), deep vein thrombosis (DVT), pulmonary embolism (PE), and death. Treatments measured were transfusion with either red blood cells (RBC) or platelets. The concurrent conditions evaluated were systemic lupus erythematosus (SLE), hepatitis C and heparin-induced thrombocytopenia (HIT). Results Out of the 115,150 hospitalized patients with ITP included in the database, 0.02% of them were diagnosed with Covid-19. The odds of a patient with Covid-19 being diagnosed with ITP were lower than those for other hospitalized patients (OR=0.860 [0.787-0.941], p=0.001). The mean age for patients with ITP diagnosed with Covid-19 was 64.1 compared to 60.9 in patients without Covid-19 (p=0.001). Hospitalized patients with ITP who were also diagnosed with Covid-19 were at a higher risk of developing epistaxis (OR: 1.45 [1.01-2.07], p=0.042), pulmonary embolism (OR: 2.22 [1.35-3.66], p=0.002), and death (OR: 4.39 [3.33-5.80], p<0.001) compared to those without Covid-19. They were not at higher odds of developing a DVT (OR: 1.25 [0.798-1.97], p=0.325), ICH (OR: 0.158 [0.0160-1.56], 0.114) or nICH (OR: 1.03 [0.678-1.55], p=0.905). They were not significantly more or less likely to get transfused with RBC (OR: 0.816 [0.585-1.14], p=0.231) or platelets (OR: 1.14 [0.865-1.53], p=0.337). The ITP patients with concurrent Covid-19 were also not more likely to suffer from SLE (OR: 0.737 [0.453-1.20], p= 0.222), Hepatitis C (OR: 0.760 [0.392-1.47], 0.416), or HIT (OR: 1.16 [0.181-7.49], p=0.872). Conclusion Hospitalized patients with Covid-19 were at a lower risk of being diagnosed with concurrent ITP than other hospitalized Covid-19 patients. Those with ITP who also had Covid 19 had significantly higher odds of complication of bleeding with epistaxis or hemoptysis as well as a higher risk of pulmonary embolism and death. However, they were not at higher risk of hemorrhage elsewhere or DVT. They were not treated with transfusions differently and having SLE, hepatitis C or HIT did not place hospitalized patients with ITP at a higher risk of developing Covid-19.

Undetected Jawbone Marrow Defects as Inflammatory and Degenerative Signaling Pathways: Chemokine RANTES/CCL5 as a Possible Link Between the Jawbone and Systemic Interactions?

BackgroundCytokines, especially chemokines, are of increasing interest in immunology. This study characterizes the little-known phenomenon of “bone marrow defects of the jawbone” (BMDJ) with known overexpression of the chemokine RANTES/CCL5 (R/C).PurposeOur investigation clarifies why BMDJ and the intensity of local R/C overexpression are challenging to detect, as examined in patients with seven different systemic immunological diseases. Specifically, we investigate whether R/C overexpression is specific to certain disease groups or if it represents a type of signal disruption found in all systemic immunological diseases.Patients and MethodsIn a total of 301 patients, BMDJ was surgically repaired during clinical practice to reduce “silent inflammation” associated with the presence of jaw-related pathologies. In each case of BMDJ, bone density was measured preoperatively (in Hounsfield units [HU]), while R/C expression was measured postoperatively. Each of the 301 patients suffered from allergies, atypical facial and trigeminal pain, or were diagnosed with neurodegenerative diseases, tumors, rheumatism, chronic fatigue syndrome, or parasympathetic disorders.ResultsIn all BMDJ cases, strongly negative HU values indicated decreased bone density or osteolysis. Consistently, all cases of BMDJ showed elevated R/C expression. These findings were consistently observed in every disease group.DiscussionBMDJ was confirmed in all patients, as verified by the HU measurements and laboratory results related to R/C expression. The hypothesis that a specific subset of the seven disease groups could be distinguished either based on the increased presence of BMDJ and by the overexpression of R/C could not be confirmed. A brief literature review confirms the importance of R/C in the etiology of each of the seven disease groups.ConclusionIn this research, the crucial role played by BMDJ and the chemokine R/C in inflammatory and immune diseases is discussed for seven groups of patients. Each specific immune disease can be influenced or propelled by BMDJ-derived R/C inflammatory signaling pathways.

P0809LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN PATIENTS WITH DIABETIC CHRONIC KIDNEY DISEASE

Abstract Background and Aims Left ventricle diastolic dysfunction (LVDD) is common cardiac changes in diabetic patients without renal insufficiency. LVDD is also frequently occurs in chronic kidney disease (CKD). Diabetic patients with CKD are at increased risk of developing cardiovascular diseases. Therefore, early detection and prevention of risk factors are critical. The aim of this study was to evaluate the impact of type 2 diabetes on left ventricular (LV) diastolic function among CKD stage 3 and 5 patients, and whether markers of fluid balance can predict LVDD. Method A total of 409 patients (age and sex matched non-diabetic CKD stage 3 [nDMCKD3], n = 106; diabetic CKD stage 3 [DMCKD3], n = 106; non-diabetic CKD stage 5 [nDMCKD5], n = 73; diabetic CKD stage 5 [DMCKD5], n = 124) were analyzed. The stage 3 CKD patients were retrospectively reviewed, and stage 5 CKD patients were prospectively analyzed. All cohort patients with stage 5 CKD were hospitalized to plan their first dialysis treatment. The following exclusion criteria were applied: ejection fraction less than 45%, history of coronary artery disease and/or intervention treatment, history of angina or myocardial infarction, abnormalities of cardiac rhythm, moderate or severe valvular heart diseases, systemic immunologic diseases, liver cirrhosis, malignancy, infection, and previous renal transplantation. Coronary artery disease having regional wall motion abnormalities on echocardiographic examination was also ruled out. Clinical and echocardiographic parameters were compared among groups. Echocardiography, bioimpedance spectroscopy, and serum NT-proBNP were analyzed in patients with stage 5 CKD. The LVDD was defined as E/é ratio greater than 15. Extracellular water/total body water (ECW/TBW) and NT-proBNP were used as markers of fluid balance. Results Patients with E/é ratio > 15 presented with more advanced stages of CKD. Prevalence of LVDD in patients with diabetes was higher compared to those without diabetes. Patients in DMCKD5 group demonstrated higher E/é ratios compared to those with nDMCKD5, DMCKD3, and nDMCKD3 (16.63±5.04 vs. 14.12±4.60 vs. 14.69±4.65 vs. 13.07±3.76, p < 0.001). The E/é ratio in patients with DMCKD5 were significantly higher than those with DMCKD3 (16.63±5.04 vs. 14.69±4.65, p = 0.003). In contrast, the E/é ratio was not significantly different between nDMCKD3 and nDMCKD5 patients (13.07±3.76 vs. 14.12±4.60, p = 0.099). The ECW/TBW in patients with DMCKD5 were significantly higher than nDMCKD5 patients (0.51±0.04 vs. 0.48±0.05, p <0.001). In a multiple regression analysis, the presence of diabetes, serum albumin level, NT-proBNP, and ECW/TBW were significantly associated with LVDD in CKD5 patients. Conclusion Our results suggest that an echocardiographic examination and assessment of volume status should routinely be performed in patients with type 2 DMCKD. Early detection of LVDD before clinical symptoms are apparent is important, regardless of the stage of DMCKD. Fluid overload could be one of the aggravating factors of LVDD in DMCKD patients. Early evaluation of volume status and control of fluid overload should be considered important therapeutic approaches for LVDD in DMCKD patients, especially for those in advanced stages.

A case report of a 40-year-old woman with endomyocardial fibrosis in a non-tropical area: from initial presentation to high urgent heart transplantation

BackgroundEndomyocardial fibrosis (EMF) represents the most common cause of restrictive cardiomyopathy worldwide. Despite a high prevalence in tropical regions, it occasionally occurs in patients who have never visited these areas. While researches have proposed various possible triggers for EMF, etiology and pathogenesis remain largely unknown. Diagnosis is based on patient history, heart failure symptoms, and echocardiographic signs of restrictive ventricular filling, atrioventricular valve regurgitation and frequently apical thrombus. Following is a case report of an Austrian patient with EMF who eventually had to undergo a heart transplant. This case report strives to promote awareness for this in non-tropical areas uncommon but nevertheless detrimental disease.Case presentationA 40-year-old woman was presented at our emergency department with chest pain and fever up to 38.1° Celsius. Plasma troponin-T levels and inflammatory markers were slightly elevated, but the echocardiogram was without pathological findings. The patient was hospitalized on the suspicion of acute myocarditis and discharged soon after improvement. Eight months later, she was presented again with chest pain and symptoms of heart failure. The echocardiogram showed normal systolic left ventricular (LV) function with LV wall thickening and severe restrictive mitral regurgitation as well as aortic and tricuspid regurgitation. Coronary angiogram was normal but right heart catheterization showed pulmonary hypertension due to left heart disease. Further diagnostic workup with cardiac magnetic resonance imaging revealed subendocardial late enhancement and apical thrombus formation in the left ventricle compatible with the diagnosis of EMF. A comprehensive diagnostic workup showed no evidence of infection, systemic immunologic or hematological disease, in particular hypereosinophilic syndrome. After a multidisciplinary consideration of several therapeutic options, the patient was listed for heart transplantation. On the waiting list, she deteriorated rapidly due to progressive heart failure and finally underwent a heart transplantation. Histological examination confirmed the diagnosis of EMF. Six years after her heart transplantation, the patient was presented in an excellent clinical condition.ConclusionsEven in non-tropical regions, the diagnosis of EMF should always be considered in restrictive cardiomyopathy. Knowledge of the distinct phenotype of EMF facilitates diagnosis, but comprehensive workup and therapeutic management remain challenging and require a multidisciplinary approach.

Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder

BackgroundIn attention deficit hyperactivity disorder (ADHD), deteriorations of brain gut axis has been shown in previous studies. One area where the most important challenges are seen in ADHD is social functioning. Zonulin is a protein found in the intestinal intraepithelial component; it has been shown that the level of zonulin increases when intestinal permeability is impaired. Changes in intestinal function were shown in ADHD. Zonulin has been shown to be associated with social impairment in children with autism spectrum disorder. In this study, it was aimed to evaluate the relationship between the ADHD symptoms and zonulin in children with ADHD. Secondarily relation of zonulin and difficulties in social functioning was examined in these children. MethodsForty children diagnosed with ADHD and forty-one healthy children similar age and gender to ADHD group and their mothers were included in the study. Children without any chronic systemic immunological or infectious diseases were included in the case and control group. The ADHD symptoms were scored by the DuPaul ADHD scale and the social functioning of the children was assessed by the Social Responsiveness Scale (SRS). Serum zonulin levels were analyzed by enzyme-linked immunosorbent assay. ResultsChildren with ADHD had higher serum zonulin levels and were more impaired in social functioning compared to controls. The level of zonulin was independently predicted with hyperactivity symptoms and SRS scores in regression analysis. ConclusionIn this sample of children with ADHD, elevated zonulin levels were associated with increased symptoms of hyperactivity and impairment of social functioning.

Aseptic-avascular osteonecrosis: local "silent inflammation" in the jawbone and RANTES/CCL5 overexpression.

Of the definitions listed in the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10), two disease descriptions can be found together: “idiopathic aseptic bone necrosis” and “avascular bone necrosis.” The relevant literature on both the conditions abbreviates both as “aseptic ischemic osteonecrosis in the jawbone” (AIOJ). To shed light on the clinical details of this condition, osteolytic jawbone samples of 24 patients with different systemic immunological diseases were examined using four steps: presurgical dental X-ray, postsurgical histology, polymerase chain reaction DNA analysis (PCR DNA) of bacteria, and RANTES/CCL5 (R/C) expression. These four steps showed that neither X-ray nor histology delivered unambiguous results with respect to inflammatory processes; furthermore, the PCR results did not show evidence of any microbial load within the jaw samples. However, there is a striking, coherent overexpression of chemokine R/C in the AIOJ samples. This study proved the aseptic existence of “silent inflammation” within the jawbone. The ICD-10 (AIOJ) definition, which is hard to interpret, can now be substantiated with clinical evidence, while the cytokine expressions described in this report can explain the systemic immunological effects observed within the group of examined patients.

Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers

Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), selected seromarkers of T regulatory (Treg), T helper (Th) and antigen-presenting cells (APC) are associated with clinical signs of disease severity and quality of life. Disease severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index, and quality of life with the Children’s Dermatology Life Quality Index (CDLQI) in AD patients ≤18 years old. Concentrations of anti-staphylococcus enterotoxin A and B immunoglobulin E (anti-SEA and anti-SEB), selected Treg/Th/APC chemokines, skin hydration and transepidermal water loss (TEWL) were measured in these patients. Forty patients with AD [median (interquartile range) age of 13.1 (7.9) years) were recruited. Backward stepwise linear regression (controlling for age, personal allergic rhinitis and asthma, and other blood markers) showed the serum anti-SEB level was positively associated with S. aureus and S. epidermidis isolations, objective SCORAD, clinical signs and CDLQI. TNF-α (a Th1 cytokine) was positively associated with objective SCORAD (B = 4.935, p = 0.010), TGF-β (a Treg cytokine) negatively with disease extent (B = −0.015, p = 0.001), IL-18 (an APC cytokine) positively with disease extent (B = 0.438, p = 0.001) and with TEWL (B = 0.040, p = 0.010), and IL-23 (an APC cytokine) negatively with disease extent (B = −2.812, p = 0.006) and positively with pruritus (B = 0.387, p = 0.007). Conclusions: Blood levels of anti-SEB, Th1, Treg and APC cytokines are correlated with various clinical signs of AD. AD is a systemic immunologic disease involving Staphylococcus aureus, cellular, humoral, cytokine and chemokine pathophysiology.

The incidence, prevalence, and outcomes of glomerulonephritis derived from a large retrospective analysis

The incidence and period prevalence of glomerulonephritis (GN) with resultant rates of death and end-stage renal disease (ESRD) in the United States are unknown. Therefore, we assessed the presumptive burden of GN ina20% Medicare sample, 5,442,495 individuals, and an Optum Clinformatics Employer Group Health Plan sample of 13,712,946 individuals. GN was established using International Classification of Diseases, Ninth Revision, Clinical Modification claims-based algorithms. Outcomes were all-cause mortality and ESRD rates. Cox proportional hazards modeling was used to determine factors associated with outcomes in incident patients. For secondary (systemic immunologic disease) and primary GN, respectively, incidence rates per 100,000 patient-years were 134 (95% CI: 132-136) and 57 (56-58) in the Medicare cohort, and 10 (9-10) and 20 (19-21) in the health plan cohort. Period prevalence per 100,000 individuals was 917 (909-952) and 306 (302-311) in Medicare and 52 (51-54) and 70 (68-71) in the health plan. Death rates in incident Medicare patients were 3.9-fold higher for secondary and 2.7-fold higher for primary GN compared with no GN. ESRD rates were typically 1 to 2 orders of magnitude higher compared with no GN. In the Medicare cohort, women withincident secondary GN were less likely than men to progress to ESRD (hazard ratio: 0.70; 95% CI: 0.62-0.80) and death (0.82; 0.79-0.86). Black patients were more likely than white patients to progress to ESRD (secondary GN, 1.56; 1.31-1.85; primary GN, 1.57; 1.35-1.83), but not to death. Thus, in the United States, GN based on health claims data is associated with increased likelihood of progression to ESRD and death.

E-PTFE Membran für die Behandlung von perforiertem Hornhautulkus

Purpose: To present the surgical management of perforated corneal ulcer using PRECLUDE® Pericardial Membrane, composed of expanded polytetrafluoroethylene (e-PTFE; GORE-TEX®), as an alternative surgical procedure in patients at high risk of graft rejections and to evaluate side effects for a prolonged period. Patients and Methods: The study included all patients who were admitted to our department and underwent surgical repair of perforated corneal ulcer with the e-PTFE membrane between 2010 and 2015. In total, 8 patients (8 eyes) were enrolled. Medical records of all patients were retrospectively reviewed. The operation was performed under peribulbar anaesthesia. Non-absorbable, microporous, watertight 0.1 mm thick e-PTFE membrane was used to close the corneal ulcer. The membrane was cut to overlap the defect adequately and to achieve the desired tissue attachment without preparing the conjunctiva or superficial trephination of the cornea. The membrane was fixed to the healthy cornea with several non-absorbable sutures (Prolene® 10.0), in order to achieve the proper stress without wrinkling. Results: Five of 8 patients were treated for systemic immunological diseases. Sjögren's syndrome was diagnosed in 2 patients, granulomatosis with polyangiitis in one, vasculitis with a history of previous sclerokeratitis in one and systemic lupus erythematosus in one. In 2 patients, corneal perforation was observed as a complication of corneal infection and in one patient as a late complication of a severe chemical burn. Corneal perforations were successfully covered with e-PTFE membrane in all patients. E-PTFE membrane was well tolerated in all patients and the eye was always preserved. After 3 to 4 months, the membrane was removed in 7 patients. The underlying cornea was thin, firm, stable and vascularised. In one patient with Sjögren's syndrome, the e-PTFE membrane is still in place. Conclusion: Surgical management of perforated corneal ulcer using E-PTFE membrane may be the method of choice for eye preservation or for delayed corneal transplantation. Our results confirmed that the procedure is safe and effective, especially in high risk patients. After removing the membrane, penetrating keratoplasty can be performed as a definitive treatment in all eyes where an improvement in visual acuity is expected.

Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye.

Uveitis, which occurs in association with systemic immunological diseases, presents a considerable medical challenge because of incomplete understanding of its pathogenesis. The signals that initiate T cells to target the eye, which may be of infectious or noninfectious origin, are poorly understood. Experimental autoimmune uveoretinitis (EAU) develops in mice immunized with the endogenous retinal protein interphotoreceptor retinoid binding protein in the presence of the adjuvant CFA. EAU manifests as posterior ocular inflammation consisting of vasculitis, granulomas, retinal damage, and invasion of self-reactive T cells, which are key clinical features of human uveitis. Our studies uncover Card9 as a critical genetic determinant for EAU. Card9 was responsible for Th17 polarization and Th17-associated Ag-specific responses, but not Th1-associated responses. Nonetheless, Card9 expression was essential for accumulation of both lineages within the eye. Consistent with its recently identified role as an intracellular signaling mediator for C-type lectin receptors (CLRs), a Card9-dependent transcriptional response in the neuroretina was observed involving genes encoding the CLRs Dectin-1, Dectin-2, and Mincle. Genetic deletion of these individual CLRs revealed an essential role for Mincle. Mincle activation was sufficient to generate the EAU phenotype, and this required activation of both Syk and Card9. In contrast, Dectin-1 contributed minimally and a possible repressive role was shown for Dectin-2. These findings extend our understanding of CLRs in autoimmune uveitis. The newly identified role of Mincle and Syk/Card9-coupled signaling axis in autoimmune uveitis could provide novel targets for treatment of patients with ocular inflammatory disease.

The Inflammatory Caspases-1 and -11 Mediate the Pathogenesis of Dermatitis in Sharpin-Deficient Mice.

Chronic proliferative dermatitis in mice (cpdm) is a spontaneous multiorgan inflammatory disorder with pathological hallmarks similar to atopic dermatitis and psoriasis in humans. Cpdm mice lack expression of SHANK-associated RH domain-interacting protein, an adaptor of the linear ubiquitin assembly complex, which acts in the NF-κB pathway to promote inflammation and protect from apoptosis and necroptosis. Although skin inflammation in cpdm mice is driven by TNF- and RIPK1-induced cell death, the contribution of initiating innate immunity sensors and additional inflammatory pathways remains poorly characterized. In this article, we show that inflammasome signaling, including the expression and activation of the inflammatory caspase-1 and -11 and IL-1 family cytokines, was highly upregulated in the skin of cpdm mice prior to overt disease onset. Genetic ablation of caspase-1 and -11 from cpdm mice significantly reduced skin inflammation and delayed disease onset, whereas systemic immunological disease persisted. Loss of Nlrp3 also attenuated skin disease, albeit more variably. Strikingly, induction of apoptosis and necroptosis effectors was sharply decreased in the absence of caspase-1 and -11. These results position the inflammasome as an important initiating signal in skin disease pathogenesis and provide novel insights about inflammasome and cell death effector cross-talk in the context of inflammatory diseases.

Oral vitamin D increases the frequencies of CD38+ human B cells and ameliorates IL‐17‐producing T cells

Vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nm) has been associated with the onset of immunological diseases including atopic dermatitis (AD), cutaneous or systemic lupus erythematosus and allergic asthma. In this study, we assessed whether oral vitamin D (cholecalciferol) supplementation leads to a systemic modulation of the phenotype of circulating lymphocyte populations and whether a defined serum 25-hydroxyvitamin D (25(OH)D) concentration can be related to the effects on lymphocytes. Cholecalciferol was administered in a dose-escalation setting to vitamin D-deficient individuals from 2000 up to 8000 IU daily for 12 weeks. Individuals without cholecalciferol intake served as controls. Peripheral B cells and T cells were examined by multicolour flow cytometric analysis. The mean serum 25(OH)D concentrations increased upon cholecalciferol intake up to 159 ± 28.7 nm, and remained low in the control group 30.0 ± 12.5 nm. Following cholecalciferol intake, the frequencies of circulating CD38 expressing B cells were significantly increased and IFN-γ+ , and/or IL-17+ CD4+ T helper cells were decreased. These data were identified to correlate with the serum 25(OH)D levels by applying two different analysis approaches (ROC and a nonlinear regression analysis). Our data indicate that increasing 25(OH)D serum concentrations are associated with an increased expression of CD38 on B cells and a decreased T-cell-dependent proinflammatory cytokine production. The therapeutical role of our findings in systemic immunological diseases should be explored in the future by further controlled clinical studies.

Anti-TNF in ocular diseases

Tumor necrosis factor-alpha (TNF-alpha) plays a role in the process of intraocular inflammation that is the cause that the use of TNF-alpha inhibitor agents is worldwide spread to treat different form of intraocular inflammations. In ophthalmology, anti-TNFs are applied in the treatment of uveitis and immune-vasculitis. The number of TNF-alpha inhibitors is increasing despite the fact that such kind of medication can be used “off-label” in the treatment of inflammations. TNF-alpha inhibitors are effective at first in that form of uveitis that is connected with systemic immunologic diseases: Mo. Behcet, rheumatoid arthritis (especially with juvenile idiopathic arthritis), Mo. Chrohn, Wegener granulomatosis, autoimmune diseases (lupus-like syndrome [LLS]). In cases of vasculitis, it can be used in giant cell arthritis, Takayasu arthritis, primary angiitis of the central nervous system, and Cogan syndrome. Anti–TNF-alpha also are effective in cases of autoimmune, noninfectious diseases of the eye: Mo. Harada, sympathetic ophthalmia. The most frequent anti–TNF-alpha that are used are etanercept, adalimumab, and infliximab. There are 3 other TNF-alpha inhibitors that are less widespread yet: golimumab, certolizumab, and tocilizumab. The advantage of the TNF-alpha inhibitors are that they have fewer side effects as corticosteroids and immunsuppressives but are more effective. Their only disadvantage: they are very expensive. None declared.

A 50-year old woman with nasal congestion, cough, and dyspnea

We present a 50-year-old woman with progressive dyspnea, cough, and nasal congestion. Evaluation revealed positive skin tests (IgE) to trees and dust mites, early glottic closure on spirometry, and sinus opacities on CT. Diagnostic considerations included allergic and nonallergic rhinitis, asthma, aspirin-exacerbated respiratory disease, vocal cord dysfunction, chronic sinusitis secondary to gastroesophageal reflux disease, and systemic inflammatory and immunologic diseases, including vasculitis. Progresson of her symptoms prompted further investigation, and a biopsy yielded an unexpected diagnosis.

Advance about cytokines in nervous systemic immunological diseases

Cytokines involve in many diseases. It' s reported that reduction or increase of cytokines is an important factor to lead to immunological diseases in nervous system. Other studies have found that certain cytokines in the different stages of the same disease play a different role. Understanding the specific mechanisms of cytokines in autoimmune diseases of the nervous system is necessary for providing theoretical basis of new ways to treat these diseases. This article will review the progress of some main cytokines in nervous systemic immunological diseases. Key words: Cytokines; Nervous system; Immunological disease

Idiopathic orbital inflammatory syndrome without pain: A case report

Background Idiopathic orbital inflammatory syndrome (IOIS) is a collection of primary orbital inflammatory expressions manifested in a variety of clinical presentations. Because the process is idiopathic, it lacks association with neoplastic, infectious, or systemic immunologic and inflammatory diseases. Therefore, an extensive analysis is required to exclude secondary etiologies of orbital inflammation. Case report Exhibited is a case of a 68-year-old white man presenting with a recent history of viral conjunctivitis and acute complaints of monocular vision loss, epiphora, photophobia, and generalized irritation without pain. On examination, he was found to have chemosis, a serous retinal detachment, and choroidal detachments. Magnetic resonance imaging found evidence of dacryoadenitis, posterior scleritis, and mild diffuse orbital inflammation. Extensive history and physical examination found no evidence of systemic inflammatory disease. IOIS was diagnosed and treated successfully with prednisone, without recurrence. Conclusions Pain is historically considered a cardinal sign of acute inflammation and a predominant symptom of IOIS. The authors present a case of acute IOIS, atypical because of its presentation in the absence of pain. In addition, a review of the literature is conducted to identify predominant clinical and radiologic characteristics of IOIS along with current accepted and proposed treatment options. Differentials are discussed to distinguish this disease from systemic immunologic and inflammatory conditions such as syphilis, sarcoidosis, and Wegener's granulomatosis as well as potentially fatal neoplastic conditions.

Hypocomplementemic Urticarial Vasculitis Syndrome

Chronic urticaria often points the way to the diagnosis of a systemic disease, particularly when urticarial vasculitis can be demonstrated. Hypocomplementemic urticarial vasculitis syndrome (HUVS) is considered to be an independent immunological disease. Selective literature review and consideration of the author's own clinical experience. The main manifestation of HUVS is chronic urticarial vasculitis with complement deficiency and the demonstration of C1q antibody in the serum. Multiple other organs are involved, sometimes severely. The diagnosis is confirmed by skin biopsy, which reveals leukocytoclastic vasculitis as a pathogenetic correlate of this systemic disease. Although HUVS is relatively rare, the medical specialists that might encounter it-ophthalmologists, rheumatologists, nephrologists, dermatologists, general practitioners, and pediatricians-should include it in their differential diagnoses whenever appropriate. Awareness of HUVS and rational diagnostic evaluation will lessen the chance of it being misdiagnosed as another type of systemic immunological disease and will reduce superfluous diagnostic testing in patients suffering from it.

Autoimmune pancreatitis: negotiating the labyrinth of terminology, diagnosis and differential diagnosis

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that typically affects adults with a male predilection. Jaundice, weight loss, anorexia and abdominal pain are the most common presenting symptoms. Serum IgG and IgG4 are frequently elevated. Imaging studies show diffuse enlargement of the pancreas with diffuse or segmental narrowing of the main pancreatic duct. When pancreatic involvement is focal, it can mimic adenocarcinoma on imaging. Histologically, the disease is characterized by a duct-centric fibroinflammatory process, dense lymphoplasmacytic infiltrates and phlebitis. High numbers of IgG4-positive plasma cells are frequently present. The absence of duct dilatation, pseudocyst, fat necrosis or calcification aids in the distinction from alcoholic pancreatitis. AIP can involve other sites in the pancreaticobilairy tree and is frequently associated with other autoimmune and fibrosclerosing diseases. This has led to the concept that AIP is the pancreatic manifestation of systemic IgG4-related immunological disease. The prognosis is generally favourable with an excellent response to steroids.

Clinical Experience of 27 Pediatric Renal Transplantation at a Single Center

Purpose: Renal transplantation is considered the treatment of choice for children with end-stage renal disease (ESRD). The results of renal transplantation were retrospectively analyzed to assess certain aspects of pediatric renal transplantation. Materials and Methods: Between January 1989 and January 2005, 27 pediatric kidney transplantations were carried out at our center. Fifteen (55.5%) patients underwent hemodialysis, two (7.4%) peritoneal dialysis and ten (37.0%) were conservative managed prior to treatment. Livingrelated donors provided 25 (92.6%) of the transplanted organs, with cadaver sources utilized for 2 (7.4%) patients. The donor age, organ source, etiology of ESRD, hospitalization period, postoperative complications, occurrence and number of acute rejections, and graft survival were assessed. Results: The causes of renal failure were chronic glomerulonephritis in 10 patients [IgA 3 nephropathy, 3 membranoproliferative glomerulonephritis (MPGN), 2 nephrotic syndrome and 2 focal segmental glomerulosclerosis (FSGS)], urinary tract anomalies in 6 (4 reflux nephropathy and 2 polycystic kidney), Alport syndrome in 1, hypertensive nephropathy in 2, systemic immunological disease in 1 and unknown causes in a further 5. Acute rejection occurred in 12 patients, all of who recovered after steroid pulse therapy. Growth and development failed in 2 patients. The postoperative complications included 4 urinary tract infections, 3 retroperitoneal hematomas, 2 lymphoceles and 1 acute ureteral obstruction. Four patients expired due to post-operative complications, such as disseminated intravascular coagulation (DIC), intracranial hematoma, sepsis and renal failure. Conclusions: Pediatric renal transplantation can be successful, even in young children with ESRD. (Korean J Urol 2007;48:72-76) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ