Seroprevalence of Toxoplasma gondii immunoglobulins and its association with systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: The exact cause of systemic lupus erythematosus (SLE) is still unknown. However, hormonal, genetic, and environmental factors may play significant roles in its development. Infection has been recognized as a crucial trigger for SLE development. Several studies have reported a higher prevalence of Toxoplasma gondii infections in patients with SLE than in healthy individuals. However, these results were inconsistent. Therefore, this study aimed to conduct a systematic review and meta-analysis of published studies to provide a definitive conclusion regarding the relationship between T. gondii infection and SLE. MATERIALS AND METHODS: We conducted a comprehensive search across diverse databases using an array of search tools to uncover pertinent literature. Following the stringent application of the inclusion and exclusion criteria, we carefully selected the appropriate reports for our meta-analysis. Using Comprehensive Meta-Analysis software v4, we analyzed the data and determined the prevalence of antibodies against T. gondii in patients affected with SLE. To investigate the correlation between T. gondii seropositivity and SLE, we computed the risk ratios (RRs) and 95% confidence intervals (CI). RESULTS: Eleven studies were considered eligible for inclusion in the present study. The prevalence of anti-IgG and IgM antibodies against T. gondii was 33.9% and 7.7%, respectively. A significant association between T. gondii IgG seropositivity and SLE was observed when compared to the controls (risk ratio = 2.14, 95% CI = 1.42 to 3.22, p = .000). However, IgM seropositivity against T. gondii was comparable between patients with SLE and healthy controls. CONCLUSIONS: In summary, this study suggests that T. gondii IgG is more prevalent in patients with SLE than in healthy individuals in areas where T. gondii infections are more frequent. However, an exact cause-and-effect relationship still needs to be established. Therefore, additional research is necessary to validate these findings and to investigate the underlying mechanisms.

Rapidly Progressive Glomerulonephritis Secondary to Immunoglobulin M-associated Monoclonal Gammopathy of Renal Significance: A Report of a Rare Case.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by monoclonal paraprotein production, with IgM and non-IgM variants. While IgM MGUS is often associated with lymphoid neoplasms, non-IgM MGUS can progress to multiple myeloma. Comorbidities include bone mineral density loss and renal complications, such as monoclonal gammopathy of renal significance (MGRS) and peripheral neuropathy. Cardiovascular risks are also elevated. Despite its significance, MGUS often goes undiagnosed due to its asymptomatic nature and overlap with age-related comorbidities. We present a case of IgM MGRS manifesting as rapidly progressive glomerulonephritis, highlighting the diagnostic challenges and clinical implications of MGUS-associated complications.

Prognostic value of serum immunoglobulin M levels in patients with acute coronary syndrome.

BACKGROUND AND AIMS: The immuno-inflammatory response is a crucial early step in the development of acute coronary syndrome (ACS). In this study, we investigated whether immunoglobulin M (IgM) in the body's initial immune response can predict the prognosis of patients with ACS. METHODS: This prospective cohort study enrolled 1556 ACS patients at Beijing Hospital between March 2017 and October 2020. All patients underwent coronary angiography (CAG). The serum IgM concentration and biochemical indicators were evaluated prior to CAG. The primary endpoint was the composite endpoint of major adverse cardiovascular and cerebrovascular events (MACCEs). Multivariate Cox proportional hazards models was used to explore the association between IgM levels and the endpoint. RESULTS: The average serum IgM levels of the population was 61.3 (42.6-88.4) mg/dL. During the median follow-up period of 55 months, 150 MACCEs occurred. Kaplan-Meier analysis showed that low serum IgM levels were associated with occurrence of MACCEs (log-rank p = 0.009). Univariate Cox proportional hazards models showed that low serum IgM (≤78.05 mg/dL) was associated with MACCEs (hazard ratio (HR) 1.648, 95 % confidence interval (CI): 1.129-2.406, p = 0.010). In patients with IgM ≤78.05 mg/dL, the HR for partially adjusted MACCEs events was 1.576 (95 % CI: 1.075-2.310) and 1.930 (95 % CI: 1.080-3.449) after adjusting for multiple covariates. The subgroup analysis showed that for patients in ≤24 BMI, never smoking and non-dyslipidemia subgroup, the lower serum IgM levels was significantly associated with the risk of MACCEs (pinteraction < 0.001, pinteraction = 0.037, pinteraction = 0.024, respectively). CONCLUSIONS: Low serum IgM levels was independently associated with MACCEs in ACS patients, especially for patients without obesity, smoking and dyslipidemia.

Early postoperative infection in patient with IgM deficiency.

Selective IgM deficiency is a rare immunological disorder, with patients presenting with recurrent infections and allergic manifestations. However, the association with early postoperative infection has not been widely reported in the literature. We describe a rare case of a patient who had an early wound infection 1 day after excision of a Merkel cell carcinoma from his right buttock and was later found to have decreased IgM levels. Selective IgM deficiency should therefore be considered in patients presenting with recurrent infections or in patients who have previously undergone surgery and subsequently developed early infection postoperatively. In this subset of patients, extra precautions may need to be taken pre- and postoperatively to reduce the risk of developing a postoperative infection.

Reference intervals for serum immunoglobulins G, M and E levels in Brazilian children aged 1 to 10 years: a population-based study

Abstract Objective: To determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1-10 years living in central Brazil. Method: A sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn's robust methods. Results: By the rank method, the IgG RI was 792-1771 mg/dL for children of both sexes aged 1-10 years. IgM RI were different for gender and age groups, being 45-196 mg/dL and 34-190 mg/dL for boys aged 1-2 years and 3-10 years, respectively. For girls, the IgM RI were 50-212 mg/dL and 39-212 mg/dL, for ages 1-4 and 5-10 years, respectively. The IgE RI for both sexes and ages 1-10 years was 6-1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn's robust method determined RI different from those obtained by previous methods. Conclusion: RI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1-10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making.

NEUT-RI, a surrogate marker of NETosis is lower in patients with strong IgM antiphospholipid antibodies.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is an acquired autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy complications. Recently, thrombotic APS was linked to increased neutrophil extracellular traps (NET) formation, suggesting an association between NETs and the severity of APS-related thrombosis. METHODS: We performed a retrospective study on patients tested for presence of antiphospholipid antibodies (990 negative and 374 positive) to evaluate the association between the neutrophil activation state, estimated by the neutrophil reactive index (NEU-RI), a parameter routinely available from some haematology analysers, and antiphospholipid antibodies. RESULTS: We do not observe a difference in NEU-RI values between positive and negative patients globally. However, interestingly, we highlight an association between high titers of IgM and low NEU-RI values indicating a lower neutrophil activation. CONCLUSION: Our data are in line with the recent questioning about the putative clinical consistency of positive solid-phase aPL IgM.

Refractory and Recurrent Skin Manifestations in an Adult With Selective Immunoglobulin M Deficiency.

Selective immunoglobulin M (IgM) deficiency (sIgMD) is a rare immunodeficiency disorder characterized by decreased serum levels of IgM. Symptoms of sIgMD include repeated infections and allergic manifestations such as asthma and allergic rhinitis. The etiology and pathology of sIgMD remain largely unknown. Moreover, no genetic cause of sIgMD and associated symptoms has been established. Herein, we describe a 47-year-old female with sIgMD who presented with repeated fevers of unknown cause since childhood. She was referred to our department because of recently developed severe dermatitis without a history of atopic dermatitis or asthma. In addition to histological evaluation by skin biopsy, immunological parameters were investigated in her peripheral blood, and the cellular immunity profile was determined by flow cytometry. The patient with refractory skin manifestations was found to have sIgMD with normal surface levels of IgM in the B cells. Along with recurrence and exacerbation in dermatitis, she showed an increase in peripheral blood eosinophils and serum IgE levels, suggesting an underlying allergic mechanism. The present case strongly indicates the importance of measuring serum IgM levels when seeing patients with recurring fever and intractable skin manifestations.

Detection of measles vaccine virus and measles-specific immunoglobulin M in children vaccinated against measles-mumps-rubella during measles outbreak.

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity.

Recent studies have demonstrated a role for Ten-Eleven Translocation-2 (TET2), an epigenetic modulator, in regulating germinal center formation and plasma cell differentiation in B-2 cells, yet the role of TET2 in regulating B-1 cells is largely unknown. Here, B-1 cell subset numbers, IgM production, and gene expression were analyzed in mice with global knockout of TET2 compared to wildtype (WT) controls. Results revealed that TET2-KO mice had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow (B-1a) and spleen (B-1b). Consistent with this finding, circulating IgM, but not IgG, was elevated in TET2-KO mice compared to WT. Analysis of bulk RNASeq of sort purified peritoneal B-1a and B-1b cells revealed reduced expression of heavy and light chain immunoglobulin genes, predominantly in B-1a cells from TET2-KO mice compared to WT controls. As expected, the expression of IgM transcripts was the most abundant isotype in B-1 cells. Yet, only in B-1a cells there was a significant increase in the proportion of IgM transcripts in TET2-KO mice compared to WT. Analysis of the CDR3 of the BCR revealed an increased abundance of replicated CDR3 sequences in B-1 cells from TET2-KO mice, which was more clearly pronounced in B-1a compared to B-1b cells. V-D-J usage and circos plot analysis of V-J combinations showed enhanced usage of VH11 and VH12 pairings. Taken together, our study is the first to demonstrate that global loss of TET2 increases B-1 cell number and IgM production and reduces CDR3 diversity, which could impact many biological processes and disease states that are regulated by IgM.

Evaluation of the local and systemic pattern of sensitization to allergens in patients with adenotonsillar hypertrophy.

PURPOSE: Adenotonsillar hypertrophy (ATH) is a medical condition characterized by the enlargement or swelling of the tonsils. The role of allergy in ATH has not been persuasively evidenced. Therefore, we investigated the state of humoral immunity and the presence of specific immunoglobulin E (sIgE) in tissues and sera in children suffering from TH. METHODS: According to the skin prick test (SPT) result, 44 ATH children were divided into the atopic and non-atopic groups. The level of sIgE against 30 inhalants and food allergens in the sera and tissue homogenates was measured by a commercial allergy immunoblotting kit. In addition, we evaluated the following variables in both tonsillar tissue homogenates and serum: total IgE, IgA, IgM, IgG, and tissue eosinophil counts. RESULTS: Our results showed that 21 (47.7%) of patients with ATH were sensitized to at least one allergen in the adenotonsillar sample and/or sera. Only two patients were negative for sIgE in the atopic group, but in the non-atopic group, only one had positive sIgE results. In the atopic group, 19 (86.4%) patients had positive sIgE in tonsillar tissues, and 18 (81.8%) had sensitized serum. There were no statistical differences in the case of other antibodies except IgE levels between the two groups. The average eosinophilic count was significantly higher in atopic patients than in the non-atopic group. CONCLUSION: The results of this study support the role of allergy in the pathogenesis of ATH and confirmed local allergic inflammation in tonsillar tissue.

Serum immunoglobulin M is associated with the severity of coronary artery disease in adults.

Purpose: The purpose of this study was to investigate the relationship between serum immunoglobulin M (IgM) and the severity of coronary artery disease in Chinese patients who underwent coronary angiography. Methods: A total of 2,045 patients who underwent coronary angiography (CAG) from March 2017 to March 2020 at Beijing Hospital were included in this study. Serum IgM concentration and biochemical indicators were measured before coronary angiography (CAG). The triquartile IgM levels at baseline in the population were analysed. Spearman rank correlation was used to analyse the association between IgM and traditional risk factors for coronary artery disease (CAD). CAD patients were divided into subgroups by affected area, number of affected vessels, and Gensini score to analyse the relationship between IgM and CAD severity. Multivariable logistic regression analysis was used to evaluate the association between IgM and CAD severity. Results: Serum IgM levels were significantly lower in the CAD group (63.5 mg/dL) than in the non-coronary artery disease (NCAD) group (72.3 mg/dL) (P < 0.001). Serum IgM levels were significantly associated with sex. Serum IgM levels were positively correlated with traditional CAD risk factors such as TG, TC and LDL-C (P < 0.05), and negatively associated with the number of obstructed vessels, the number of affected areas, and Gensini scores. After adjusting for age, sex, smoking status, hypertension, dyslipidaemia, diabetes, stroke, and statin use history, a high IgM level was independently negatively associated with the severity of CAD expressed by the Gensini score. Conclusion: We determined that serum IgM was independently negatively associated with the severity of CAD diagnosed by angiography in Chinese adults.

Supportive Treatment of a Dog with Leishmaniosis and Severe Glomerulopathy with Immunoadsorption.

A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general condition and moderately enlarged mandibular and popliteal lymph nodes. The initial blood work showed severe azotemia and hypoalbuminemia. In the urinalysis, marked proteinuria with a urine protein/creatinine ratio (UPC) of 4.69 was found. Further workup showed a high leishmania antibody titer. The dog was diagnosed with leishmaniosis and glomerulonephritis. Initial treatment consisted of intravenous fluid therapy, allopurinol, miltefosine, amlodipine, clopidogrel, and a diet with a low purine content. Creatinine temporarily decreased but increased again after three days. For further supportive treatment, intermittent hemodialysis in combination with hemoperfusion with the cytosorb® adsorber was performed. A total blood volume of 17.7 L was processed within three hours. Thereafter, immunoadsorption (IA) was performed with the COM.TEC® and ADAsorb® platforms and a LIGASORB® adsorber to eliminate circulating immunocomplexes. Treatment time for IA was two hours with a blood flow of 50 mL/min. A total plasma volume of 2.4 L was processed. Over the following days, creatinine declined, and the patient improved significantly. UPC decreased to 1.74 on day 17 after IA. The patient was discharged after two and a half weeks. Two years after the initial event, the patient is still in excellent condition, with creatinine, UPC, and albumin levels in the reference range. Therefore, IA might be an additional therapeutic option for dogs with leishmaniosis-induced glomerulonephritis and subsequent severe azotemia to improve immunocomplex-mediated glomerulonephritis.

Analysis of glomerular deposition of IgM and C3 in patients with podocytopathies.

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are the main causes of nephrotic syndrome in the world. The complement system appears to play an important role in the pathogenesis of these diseases. To evaluate the deposition of immunoglobulins and particles of the complement system in renal biopsies of patients with FSGS and MCD and relate to laboratory data, we selected 59 renal biopsies from patients with podocytopathies, 31 from patients with FSGS and 28 with MCD. Epidemiological, clinical, laboratory information and the prognosis of these patients were evaluated. Analysis of the deposition of IgM, IgG, C3, C1q and C4d in renal biopsies was performed. We related IgM and C3 deposition with laboratory parameters. Statistical analysis was performed using GraphPad Prism version 7.0. Glomerular deposition of IgM was significantly higher in the FSGS group, as was codeposition of IgM and C3. The clinical course of patients and laboratory data were also worse in cases of FSGS, with a higher percentage progressing to chronic kidney disease and death. Patients with C3 deposition had significantly higher mean serum creatinine and significantly lower eGFR, regardless of disease. Patients with FSGS had more IgM and C3 deposition in renal biopsies, worse laboratory data and prognosis than patients with MCD. C3 deposition, both in FSGS and MCD, appears to be related to worsening renal function.

The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia A.

Objectives: Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities. Methods: All persons with hemophilia A (mild (FVIII > 5-40 IU/dL)/moderate [FVIII 1-5 IU/dL)/severe (FVIII < 1 IU/dL)] with an available plasma sample who participated in the sixth Hemophilia in the Netherlands study between 2018 and 2019 were included. The presence of anti-FVIII antibodies of the immunoglobulin A, M, and G isotypes and IgG subclasses, along with antibody titer levels, were assessed using direct-binding ELISAs. FVIII specificity was assessed using a competition-based ELISA approach. The inhibitor status was determined using the Nijmegen ultra-sensitive Bethesda assay (NusBA) and the Nijmegen Bethesda assay (NBA). Results: In total, 788 persons with hemophilia A (336 (42.6%) mild, 123 (15.6%) moderate, 329 (41.8%) severe hemophilia) were included. The median age was 45 years (IQR 24-60), and the majority (50.9%) had over 150 exposure days to FVIII concentrates. Within our population, 144 (18.3%) individuals had non-neutralizing FVIII-specific antibodies, 10 (1.3%) had very low-titer inhibitors (NusBA positive; NBA negative), and 13 (1.6%) had inhibitors (both NusBA and NBA positive). IgG1 was the most abundant FVIII-specific antibody subclass, and the highest titer levels were found for IgG4. In individuals without a reported history of inhibitor development, no clear differences were observed in antibody patterns between those who were minimally or highly exposed to FVIII concentrates. IgG4 subclass antibodies were only observed in persons with a reported history of FVIII inhibitor or in those with a currently detected (very low-titer) inhibitor. Conclusion: In this cross-sectional study, we identified non-neutralizing antibodies in a relatively large proportion of persons with hemophilia A. In contrast, in our population, consisting of persons highly exposed to FVIII concentrates, (very low-titer) inhibitors were detected only in a small proportion of persons, reflecting a well-tolerized population. Hence, our findings suggest that only a small subpopulation of non-neutralizing FVIII-specific antibodies is associated with clinically relevant inhibitors.

Relevance of Polymerase Chain Reaction in Early Diagnosis of Leptospirosis.

Aim and background: Leptospirosis is common in India, especially in the southern states. Mortality is high among untreated cases. Diagnosis of leptospirosis remains a challenge in India as polymerase chain reaction (PCR), which is more sensitive than Immunoglobulin M (IgM) is not widely available. This study aimed to find out the difference in diagnostic yield with PCR and IgM in early leptospirosis. Materials and methods: This retrospective, single-center study included 67 adults with laboratory-confirmed leptospirosis (IgM, PCR, or both) who presented within 7 days of symptom onset and were admitted to the intensive care unit (ICU). The difference in the diagnostic yield with PCR and IgM ELISA was studied. Results: About 77.6% of the patients tested positive by PCR and 55.2% tested positive by IgM. There was a statistically significant difference in the detection of leptospirosis by PCR and IgM (p-value = 0.036). In the subgroup of patients who presented within 3 days of onset of symptoms, PCR positivity was 90.32% whereas IgM positivity was only 25.8%. Conclusion: Our study showed that the sensitivity of leptospira PCR is significantly higher than IgM in the first week of illness. It also showed that among the subset of patients who died, a majority were detected only by PCR. Since PCR is not widely available, leptospirosis remains underdiagnosed and mortality from the same is underestimated. Polymerase chain reaction, if routinely done along with IgM for all suspected cases of leptospirosis that present within the first week of illness helps in prompt diagnosis and treatment. How to cite this article: Sreevalsan TV, Chandra R. Relevance of Polymerase Chain Reaction in Early Diagnosis of Leptospirosis. Indian J Crit Care Med 2024;28(3):290-293.

A Specific Pattern of Routine Cerebrospinal Fluid Parameters Might Help to Identify Cases of West Nile Virus Neuroinvasive Disease.

BACKGROUND: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus. METHODS: Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME. RESULTS: In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood-CSF-barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%). CONCLUSIONS: Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV.

Evaluation of potential antiviral activities of antimicrobial peptides in fish mucus.

BACKGROUND: Fish skin mucus contains innate immune factors and acts as the first line of physical or chemical defense against pathogens. OBJECTIVE: The primary aim of this study was to determine the antiviral activity of sea bream (SBr), rainbow trout (RT), and sea bass (SBa) fish skin mucus against herpes simplex virus (HSV)-1. In addition, it was aimed to associate possible antiviral activity with antimicrobial peptides (AMPs) such as cathelicidin, hepcidin, galectin 2, and C10ORF99, whose levels were determined in the mucus. METHODS: The antiviral activity and oxidative/antioxidant status of mucus against HSV-1 virus was evaluated. In addition, AMPs, SOD, and CAT activities, and immunoglobulin M levels were also analyzed in mucus of fish. RESULTS: Antiviral activity mucus of SBr, RT, and SBa against HSV-1 were determined as 2-4, 2-5, and 2-2, respectively. The higher antiviral activity of SBr and RT mucus compared to the mucus of SBa can be associated with higher AMP levels in them. CONCLUSION: The skin mucus of SBr and RT may be nutritional supplement, adjuvant, and a new agent that can potentiate the effects of antimicrobial/antiviral agents.

Peritoneal B Cells Play a Role in the Production of Anti-polyethylene Glycol (PEG) IgM against Intravenously Injected siRNA-PEGylated Liposome Complexes.

Polyethylene glycol (PEG)-modified (PEGylated) cationic liposomes are frequently used as delivery vehicles for small interfering RNA (siRNA)-based drugs because of their ability to encapsulate/complex with siRNA and prolong the circulation half-life in vivo. Nevertheless, we have reported that subsequent intravenous (IV) injections of siRNA complexed with PEGylated cationic liposomes (PLpx) induces the production of anti-PEG immunoglobulin M (IgM), which accelerates the blood clearance of subsequent doses of PLpx and other PEGylated products. In this study, it is interesting that splenectomy (removal of spleen) did not prevent anti-PEG IgM induction by IV injection of PLpx. This indicates that B cells other than the splenic version are involved in anti-PEG IgM production under these conditions. In vitro and in vivo studies have shown that peritoneal cells also secrete anti-PEG IgM in response to the administration of PLpx. Interleukin-6 (IL-6) is a glycoprotein that is secreted by peritoneal immune cells and has been detected in response to the in vivo administration of PLpx. These observations indicate that IV injection of PLpx stimulates the proliferation/differentiation of peritoneal PEG-specific B cells into plasma cells via IL-6 induction, which results in the production of anti-PEG IgM from the peritoneal cavity of mice. Our results suggest the mutual contribution of peritoneal B cells as a potent anti-PEG immune response against PLpx.

Comparison between characteristics of immunoglobulin M nephropathy and other glomerular diseases.

Background: Immunoglobulin M (IgM) nephropathy (IgMN) is characterized by the IgM deposition in the kidney's mesangium. We assessed the impact of electron-dense deposits (EDDs) on IgMN and compared it to other kidney diseases. Methods: We enrolled 63 adult patients with IgMN who underwent renal biopsy from May 2003 to June 2017. We compared clinicopathological features of IgMN based on EDD presence; compared characteristics to 91 minimal change disease (MCD), 103 focal segmental glomerulosclerosis (FSGS), and 469 immunoglobulin A nephropathy (IgAN) patients. Renal events were defined as a >50% decrease in estimated glomerular filtration rate (eGFR), eGFR of <15 mL/min/1.73 m2, or end-stage renal disease development. Results: IgMN patients with EDDs had increased mesangial cellularity, matrix accumulation, prominent immunofluorescent staining, and more diffuse podocyte effacement than those without EDD. Clinical characteristics and renal outcomes did not differ significantly based on EDD presence. During 79.5 ± 58.8 months of follow-up, renal events developed in 46.2% and 46.0% of IgMN cases with and without EDD. IgMN (46.0%) and FSGS cases (40.8%) had similar frequencies of renal events and higher frequency than MCD (18.7%) or IgAN cases (26.4%). IgMN cases had more severe manifestations than MCD and IgAN; higher blood pressure, lower proteinuria, and eGFR levels at biopsy than MCD cases; higher blood pressure, proteinuria, frequency of acute kidney injury, and lower eGFR levels. Conclusion: Clinical characteristics of IgMN did not differ based on EDD presence. Therefore, IgMN should be defined based on IF findings. IgMN shared clinical characteristics with FSGS but had more severe than MCD and IgAN.