Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complexmediated glomerulonephritis: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P < 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P < 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P < 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Complement Protection Against Immune Complex and Acute Glomerulonephritis

in this study serum complement mediated immune complex solubilizing capacity (CMSC) and immune complement precipitation capacity (ICPIC) of 32 children with acute glomerulonephritis (AGN) were measured. The data showed that the level of serum CMSC and ICPIC was markedly decreased in acute phase and returned to normal in the 7th week after onset of disease.Correlation analysis revealed that there were positive correlation between the level of serum CMSC and ICPIC and the serum concentration of CH50, C3, C4, but no linear correlation between the level of serum CMSC and ICPIC and the amount of CIC. These results suggest that the declined serum CMSC and ICPIC in AGN may be associ ated with the pathogenesis of AGN.

Immune-mediated neuromuscular complications after haploidendtical hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation （Allo-HSCT） is associated with neuromuscluar complications in fewer than 5% of patients.1 The most common causes are associated with the toxicity of the conditioning regimen,infections,bleeding,and malignant disease relapse.Allo-HSCT related neuromuscular complications can also be caused by immune-mediated mechanisms,which are usually present in the form of myositis/polymyositis or demyelinating polyneuropathy.Keywords：allogeneic hematopoietic stem cell transplantation; immune mediated; chronic demyelinating polyneuropathy;steroid myopathy

Global properties of a cell mediated immunity in HIV infection model with two classes of target cells and distributed delays

In this paper, we study the global properties of a human immunodeficiency virus （HIV） infection model with cytotoxic T lymphocytes （CTL） immune response. The model is a six-dimensional that describes the interaction of the HIV with two classes of target cells, CD4＋ T cells and macrophages. The infection rate is given by saturation functional response. Two types of distributed time delays are incorporated into the model to describe the time needed for infection of target cell and virus replication. Using the method of Lyapunov functional, we have established that the global stability of the model is determined by two threshold numbers, the basic infection reproduction number R0 and the immune response activation number R0. We have proven that if R0 ≤ 1, then the uninfected steady state is globally asymptotically stable （GAS）, if R0≤ 1 〈 R0, then the infected steady state without CTL immune response is GAS, and if R0〉 1, then the infected steady state with CTL immune response is GAS.

Manipulation of the immune system by non-small cell lung cancer and possible therapeutic interference

Pulmonary carcinomas have developed mechanisms by which they escape the attack of immune cells.Immune checkpoint molecules programmed death 1-programmed death ligand 1(PD1-PDL1)and the cytotoxic T-lymphocyte antigen 4 system have gained attention.The expression of PDL1 by tumor cells causes immune tolerance,and further influences the microenvironment via orchestration by cytokines.Therapy with PDL1 antibodies could restore the cytotoxicity of T-lymphocytes towards tumor cells.Many patients will respond to this treatment.However,resistance mechanisms will counteract this therapy.New investigations have identified additional immune checkpoint inhibitors such as lymphocyte activation gene 3 and T cell immunoglobulin and mucin-domain containing-3.Tumor cells also induce tolerance by manipulating cells of the innate immune system.Macrophages are polarized to tumor-friendly M2,neutrophils into N2 types,and dendritic cells and myeloid suppressor cells are switched to assist tumor cells.Regulatory T cells enter the tumor microenvironment and signal tolerance to cytotoxic cells,inhibiting the influx of NK cells.Soluble mediators either released by tumor cells or cells of the tumor stroma induce immune tolerance,examples including tryptophan and indolamine dioxygenases,arginine and adenosine.Treatment options to counteract these molecules are currently being tested.The tumor stroma has been classified as immune-inflamed,immune-excluded,and immune-desert types.The latter might be switched to an inflamed type by induction of tertiary lymph follicles.Dendritic cells and macrophages normally phagocytose tumor antigens,but inhibitors of phagocytosis can block this.Interference with these molecules is another option for re-establishing the cytotoxic action of the immune system against tumor cells.In this review we will discuss these aspects with a special emphasis on non-small cell lung cancer.

Increased interleukin-6 is associated with long COVID-19:a systematic review and meta-analysis

Background Coronavirus disease 2019(COVID-19)can involve persistence,sequelae,and other clinical complications that last weeks to months to evolve into long COVID-19.Exploratory studies have suggested that interleukin-6(IL-6)is related to COVID-19;however,the correlation between IL-6 and long COVID-19 is unknown.We designed a systematic review and meta-analysis to assess the relationship between IL-6 levels and long COVID-19.Methods Databases were systematically searched for articles with data on long COVID-19 and IL-6 levels published before September 2022.A total of 22 published studies were eligible for inclusion following the PRISMA guidelines.Analysis of data was undertaken by using Cochran's Q test and the Higgins I-squared(I2)statistic for heterogeneity.Random-effect meta-analyses were conducted to pool the IL-6 levels of long COVID-19 patients and to compare the differences in IL-6 levels among the long COVID-19,healthy,non-postacute sequelae of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection(non-PASC),and acute COVID-19 populations.The funnel plot and Egger's test were used to assess potential publication bias.Sensitivity analysis was used to test the stability of the results.Results An increase in IL-6 levels was observed after SARS-CoV-2 infection.The pooled estimate of IL-6 revealed a mean value of 20.92 pg/ml(95%CI=9.30–32.54 pg/ml,I2=100%,P<0.01)for long COVID-19 patients.The forest plot showed high levels of IL-6 for long COVID-19 compared with healthy controls(mean difference=9.75 pg/ml,95%CI=5.75–13.75 pg/ml,I2=100%,P<0.00001)and PASC category(mean difference=3.32 pg/ml,95%CI=0.22–6.42 pg/ml,I2=88%,P=0.04).The symmetry of the funnel plots was not obvious,and Egger’s test showed that there was no significant small study effect in all groups.Conclusions This study showed that increased IL-6 correlates with long COVID-19.Such an informative revelation suggests IL-6 as a basic determinant to predict long COVID-19 or at least inform on the“early stage”of long COVID-19.