Ig Isotypes Research Articles

Monoclonal Gammapathy of Renal Significance: Morphological Variants of Lesion

The article discusses the concept of monoclonal renal gammopathy, which combines various renal diseases caused by the deposition of monoclonal immunoglobulin and / or their components in the glomeruli and tubulointerstitium. This nosological group was identified within the group of monoclonal gammopathies of undetermined significance (in 2012). The data on the study of morphological kidney damage associated with monoclonal renal gammopathy are presented. The spectrum of renal diseases in monoclonal renal gammopathy is diverse, and its classification is based on the localization of renal lesions in the glomeruli, tubules, vascular interstitium and stroma, as well as the peculiarity of the deposition of immunoglobulins (organized and unorganized). Kidney biopsy is required in most cases to locate the lesion, assess its severity, and predict patient survival. Diagnostics requires the integration of morphological changes using light microscopy, immunofluorescence, electron microscopy, and in some cases, staining of monoclonal protein for Ig isotypes is used (staining with hematoxylin / eosin, Schiff stain (PAS reaction), Jones stain, Congo Red stain, Masson’s trichromal stain). Early diagnosis and timely prescription of clone-oriented therapy by a hematologist and / or a hematooncologist can stop the progression of the malignant process and kidney malfunction. A nephrologist should monitor the patient, interacting with the hematologist.

Targeting TIGIT for Immunotherapy of Cancer: Update on Clinical Development.

Immune checkpoint blockers have dramatically improved the chances of survival in patients with metastatic cancer, but only a subset of the patients respond to treatment. Search for novel targets that can improve the responder rates and overcome the limitations of adverse events commonly seen with combination therapies, like PD-1 plus CTLA-4 blockade and PD-1/PD-L1 plus chemotherapy, led to the development of monoclonal antibodies blocking T-cell immunoglobulin and ITIM domain (TIGIT), a inhibitory checkpoint receptor expressed on activated T cells and NK cells. The strategy showed potential in pre-clinical and early clinical studies, and 5 molecules are now in advanced stages of evaluation (phase II and above). This review aims to provide an overview of clinical development of anti-TIGIT antibodies and describes the factors considered and thought process during early clinical development. Critical aspects that can decide the fate of clinical programs, such as origin of the antibody, Ig isotype, FCγR binding, and the dose as well as dosing schedule, are discussed along with the summary of available efficacy and safety data from clinical studies and the challenges in the development of anti-TIGIT antibodies, such as identifying patients who can benefit from therapy and getting payer coverage.

Single-reaction multi-antigen serological test for comprehensive evaluation of SARS-CoV-2 patients by flow cytometry.

Here, we describe a new, simple, highly multiplexed serological test that generates a more complete picture of seroconversion than single antigen‐based assays. Flow cytometry is used to detect multiple Ig isotypes binding to four SARS‐CoV‐2 antigens: the Spike glycoprotein, its RBD fragment (the main target for neutralizing antibodies), the nucleocapsid protein, and the main cysteine‐like protease in a single reaction. Until now, most diagnostic serological tests measured antibodies to only one antigen and in some laboratory‐confirmed patients no SARS‐CoV‐2‐specific antibodies could be detected. Our data reveal that while most patients respond against all the viral antigens tested, others show a marked bias to make antibodies against either proteins exposed on the viral particle or those released after cellular infection. With this assay, it was possible to discriminate between patients and healthy controls with 100% confidence. Analysing the response of multiple Ig isotypes to the four antigens in combination may also help to establish a correlation with the severity degree of disease. A more detailed description of the immune responses of different patients to SARS‐CoV‐2 virus might provide insight into the wide array of clinical presentations of COVID‐19.

Immunoglobulin subtype-coated bacteria are correlated with the disease activity of inflammatory bowel disease

Immune response involving various immunoglobulin (Ig) isotypes and subtypes to microbiome is involved in the pathogenesis and disease activity of inflammatory bowel diseases (IBDs). To clarify the presence of Ig-coated bacteria in the intestine and its association with disease activity in ulcerative colitis (UC) and Crohn’s disease (CD), we extracted and classified Ig-coated bacteria from fecal samples of 42 patients with IBD and 12 healthy controls (HCs) using flow cytometry and 16S ribosomal RNA sequence analysis. The percentage of bacteria coated with IgA and IgM was higher in patients with IBD than in HCs, and IgG-coated bacteria were found only in patients with IBD. Moreover, the percentages of bacteria coated with IgG1, IgG2, IgG3, and IgM in UC samples and IgG3, IgG4, and IgM in CD samples were correlated with disease activities. The proportions of Bacteroides ovatus and Streptococcus increased during the active phase of CD. Hence, the detailed analysis of Ig-coated bacteria and Ig subtypes using flow cytometry could aid in developing useful indicators of disease activity and identifying more disease-related bacteria, which could become novel treatment targets for IBDs.

Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?

Recently, recombinant monoclonal antibodies (mAbs) of three Ig isotypes (IgG, IgA, and IgM) sharing the same anti-spike protein Fab region were developed; we evaluated their neutralizing abilities using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein and ACE2-transfected Crandell–Rees feline kidney cells as the host cell line. Although each of the anti-SARS-CoV-2 mAbs was able to neutralize the spike-coated lentiviruses, IgM and IgA neutralized the viral particles at 225-fold and 125-fold lower concentrations, respectively, than that of IgG. Our finding that the neutralization ability of Igs with the same Fab domain was dramatically higher for IgM and IgA than IgG mAbs suggests a strategy for developing effective and affordable antibody therapies for COVID-19. The efficient neutralization conferred by IgM and IgA mAbs can be explained by their capacity to bind multiple virions. While several IgG mAbs have been approved as therapeutics by the FDA, there are currently no IgM or IgA mAbs available. We suggest that mAbs with multiple antigen-binding sites such as IgM and IgA could be developed as the new generation of therapy.

Critically Ill COVID-19 Patients Exhibit Anti-SARS-CoV-2 Serological Responses.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health care emergency. Anti-SARS-CoV-2 serological profiling of critically ill COVID-19 patients was performed to determine their humoral response. Blood was collected from critically ill ICU patients, either COVID-19 positive (+) or COVID-19 negative (−), to measure anti-SARS-CoV-2 immunoglobulins: IgM; IgA; IgG; and Total Ig (combined IgM/IgA/IgG). Cohorts were similar, with the exception that COVID-19+ patients had a greater body mass indexes, developed bilateral pneumonias more frequently and suffered increased hypoxia when compared to COVID-19- patients (p < 0.05). The mortality rate for COVID-19+ patients was 50%. COVID-19 status could be determined by anti-SARS-CoV-2 serological responses with excellent classification accuracies on ICU day 1 (89%); ICU day 3 (96%); and ICU days 7 and 10 (100%). The importance of each Ig isotype for determining COVID-19 status on combined ICU days 1 and 3 was: Total Ig, 43%; IgM, 27%; IgA, 24% and IgG, 6%. Peak serological responses for each Ig isotype occurred on different ICU days (IgM day 13 > IgA day 17 > IgG persistently increased), with the Total Ig peaking at approximately ICU day 18. Those COVID-19+ patients who died had earlier or similar peaks in IgA and Total Ig in their ICU stay when compared to patients who survived (p < 0.005). Critically ill COVID-19 patients exhibit anti-SARS-CoV-2 serological responses, including those COVID-19 patients who ultimately died, suggesting that blunted serological responses did not contribute to mortality. Serological profiling of critically ill COVID-19 patients may aid disease surveillance, patient cohorting and help guide antibody therapies such as convalescent plasma.

Impact of Nematode Infections on Non-specific and Vaccine-Induced Humoral Immunity in Dual-Purpose or Layer-Type Chicken Genotypes.

Nematode infections may induce immune-modulatory effects and influence host-immune responses to other pathogens. The aim of the study was to investigate whether a mixed nematode-infection influences non-specific and vaccine-induced humoral immunity against Newcastle Disease Virus (NDV), Infectious Bronchitis Virus (IBV), and Avian Metapneumovirus (AMPV) in already vaccinated hens of a dual-purpose (Lohmann Dual, LD) or a layer genotype (Lohmann Brown Plus; LB). Until 17 weeks-of-age, LD (n = 70) and LB (n = 109) hens were vaccinated against major bacterial and viral diseases and coccidiosis. At 24 weeks-of-age, the hens received either a placebo or an oral inoculation of 1,000 infectious eggs of A. galli and H. gallinarum. Plasma total immunoglobulin (Ig) isotypes (IgY, IgM, IgA) levels and vaccine-induced antibody titers against NDV, IBV, and AMPV were determined from 2 to 18 weeks post-infection (wpi). Infections had no suppressing effect on total Ig isotypes IgY, IgM, and IgA as well as on vaccine-induced antibody titers against NDV, IBV, and AMPV (P > 0.05). Overall, LB hens had higher levels of IgY, IgM, and IgA than those of LD hens (P < 0.05). There were no differences between IBV titers of the two genotypes (P > 0.05). Independent of infection status of the hens, NDV titers were higher in LB hens than in LD hens at wpi 2 (P < 0.05), but not in following weeks (P > 0.05). Uninfected LD hens had lower AMPV titers than their infected counterparts at 6 and 14 wpi (P < 0.05). Regardless of nematode infection, LD hens revealed a higher risk of responding weak to vaccination against NDV (odds ratio = 5.45; P = 0.021) and AMPV (odds ratio = 13.99, P < 0.001) than did LB hens (P > 0.05). We conclude that nematode infections have no adverse effects on non-specific and vaccine-induced humoral immunity in either genotype. LB hens have higher levels of total immunoglobulin isotypes than LD hens. Except for IBV, vaccine-induced humoral immune responses show a dependency on genotype. Dual-purpose hens show lower responsiveness to vaccinations against NDV and AMPV, possibly due to factors associated with increased body fat reserves in this genotype.

Development of anti-human IgM nanobodies as universal reagents for general immunodiagnostics

Nanobodies are the smallest antibody fragments which bind to antigens with high affinity and specificity. Due to their outstanding physicochemical stability, simplicity and cost-effective production, nanobodies have become powerful agents in therapeutic and diagnostic applications. In this work, the advantages of nanobodies were exploited to develop generic and standardized anti-human IgM reagents for serology and IgM+ B-cell analysis. Selection of anti-IgM nanobodies was carried out by evaluating their yields, stability, binding kinetics and cross-reactivity with other Ig isotypes. High affinity nanobodies were selected with dissociation constants (KDs) in the nM range and high sensitivities for detection of total IgM by ELISA. The nanobodies also proved to be useful for capturing IgM in the serodiagnosis of an acute infection as demonstrated by detection of specific IgM in sera of dengue virus patients. Finally, due to the lack of an Fc region, the selected nanobodies do not require Fc receptor blocking steps, facilitating the immunophenotyping of IgM+ cells by flow cytometry, an important means of diagnosis of immunodeficiencies and B-cell lymphoproliferative disorders. This work describes versatile anti-IgM nanobodies that, due to their recombinant nature and ease of reproduction at low cost, may represent an advantageous alternative to conventional anti-IgM antibodies in research and diagnosis.

CD200R1 and CD200R1L expression is regulated during B cell development in swine and modulates the Ig production in response to the TLR7 ligand imiquimoid.

The CD200R family comprises a group of paired receptors that can modulate the activation of immune cells. They are expressed both on myeloid cells and lymphocyte subsets. Here we report that the expression of these receptors on porcine B cells is tightly regulated, being mainly expressed on mature cells. The expression of the inhibitory receptors CD200R1 and/or its splicing variant CD200R1X2, either in combination or not with the activating receptor CD200R1L, is upregulated in sIgM+ effector/memory cells, and tends to decline thereafter as these cells progress to plasmablasts or switch the Ig isotype. sIgM+ naïve and primed cells only express, by contrast, the CD200R1X2 receptor. B-1 like cells also express CD200R1 isoforms, either alone or in combination with CD200R1L. Treatment of peripheral blood mononuclear cells with a monoclonal antibody specific for inhibitory receptors, enhances the IgM and IgG production induced by TLR7 stimulation suggesting a modulatory role of B cell functions of these receptors.

Epigenetic regulation of IgA class-switching by miR-146a through selective downregulation of Smad2, Smad3 and Smad4

Abstract IgA is the predominant antibody isotype at mucosal surfaces. It plays a critical role in mucosal homeostasis and provides a first line of defense in immune protection. Class switch DNA recombination (CSR) to IgA is initiated by TGF-β, which induces Smad2, Smad3, Smad4 and Runx3 binding to the Iα promoter. This promotes germline Iα-Cα transcription, thereby increasing accessibility to the Igα locus. Epigenetic modifications, such as microRNAs, have been shown to modulate the antibody response, although the role of microRNAs in B cell differentiaton processes, such as guiding CSR to specific Ig isotypes, remains unexplored. miR146a has been shown to regulate T cell, dendritic cell and macrophage functions in innate and adaptive immune responses. Here we show that miR146a, which targets Smad2, Smad3 and Smad4 3′UTRs and is the most abundant miRNA in resting B cells, is significantly downregulated in B cells undergoing CSR to IgA. Deletion of miR146a, as in miR146a−/− B cells, frees Smad2, Smad3 and Smad4 from transcriptional repression, thereby increasing recruitment of these transcription factors to the Iα promoter. This results in increased germline Iα-Cα transcription and CSR to IgA without alterations to Aicda and Prdm1 expression. Accordingly, miR146a−/− mice displayed an elevated gut, systemic IgA responses and kidney IgA deposition, a hallmark of hyper IgA nephropathy. This was recapitulated in μMT/miR146a−/− mixed bone marrow chimera mice, further demonstrating the B cell-intrinsic role of miR146a in the modulation of CSR to IgA. Thus, by silencing Smad2, Smad3 and Smad4 transcription, miR-146a plays an important B cell intrinsic role in the modulation of the IgA response.

From Multiplex Serology to Serolomics-A Novel Approach to the Antibody Response against the SARS-CoV-2 Proteome.

The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays to assess SARS-CoV-2 epidemiology. We, therefore, aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody responses to the SARS-CoV-2 proteome. Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance was assessed in a COVID-19 case cohort (n = 48 hospitalized patients from Heidelberg) as well as n = 85 age- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial enzyme-linked immunosorbent (ELISA) assays. A sensitivity of 100% (95% CI: 86–100%) was achieved in COVID-19 patients 14 days post symptom onset with dual sero-positivity to SARS-CoV-2 N and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96–100%). Antibody responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody response. This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero-prevalence.

The Characterization of Disease Severity Associated IgG Subclasses Response in COVID-19 Patients.

Increasing evidence suggests that dysregulated immune responses are associated with the clinical outcome of coronavirus disease 2019 (COVID-19). Nucleocapsid protein (NP)-, spike (S)-, receptor binding domain (RBD)- specific immunoglobulin (Ig) isotypes, IgG subclasses and neutralizing antibody (NAb) were analyzed in 123 serum from 63 hospitalized patients with severe, moderate, mild or asymptomatic COVID-19. Mild to modest correlations were found between disease severity and antigen specific IgG subclasses in serum, of which IgG1 and IgG3 were negatively associated with viral load in nasopharyngeal swab. Multiple cytokines were significantly related with antigen-specific Ig isotypes and IgG subclasses, and IL-1β was positively correlated with most antibodies. Furthermore, the old patients (≥ 60 years old) had higher levels of chemokines, increased NAb activities and SARS-CoV-2 specific IgG1, and IgG3 responses and compromised T cell responses compared to the young patients (≤ 18 years old), which are related with more severe cases. Higher IgG1 and IgG3 were found in COVID-19 patients with comorbidities while biological sex had no effect on IgG subclasses. Overall, we have identified diseases severity was related to higher antibodies, of which IgG subclasses had weakly negative correlation with viral load, and cytokines were significantly associated with antibody response. Further, advancing age and comorbidities had obvious effect on IgG1 and IgG3.

Framework for Characterizing Longitudinal Antibody Response in Children After Plasmodium falciparum Infection.

Human Plasmodium infection produces a robust adaptive immune response. Time courses for 104 children followed for 42 days after initiation of Plasmodium falciparum chemotherapy were assayed for antibody levels to the five isotypes of human immunoglobulins (Ig) and 4 subclasses of IgG for 32 P. falciparum antigens encompassing all 4 parasite stages of human infection. IgD and IgE against these antigens were undetectable at 1:100 serum concentration, but other Ig isotypes and IgG subclasses were consistently observed against all antigens. Five quantitative parameters were developed to directly compare Ig response among isotypes and antigens: Cmax, maximum antibody level; ΔC, difference between Cmax and the antibody level at Day 0; tmax, time in days to reach Cmax; t1/2, Ig signal half-life in days; tneg, estimated number of days until complete loss of Ig signal. Classical Ig patterns for a bloodborne pathogen were seen with IgM showing early tmax and IgG production highest among Ig isotypes. However, some unexpected trends were observed such as IgA showing a biphasic pattern for many antigens. Variability among these dynamics of Ig acquisition and loss was noted for different P. falciparum antigens and able to be compared both quantitatively and statistically. This parametrization methodology allows direct comparison of Ig isotypes produced against various Plasmodium antigens following malaria infection, and the same methodology could be applied to other longitudinal serologic studies from P. falciparum or different pathogens. Specifically for P. falciparum seroepidemiological studies, reliable and quantitative estimates regarding the IgG dynamics in human populations can better optimize modeling efforts for serological outputs.

Prevailing Role of Mucosal Igs and B Cells in Teleost Skin Immune Responses to Bacterial Infection.

The skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent Ig in SALT have only been reported upon infection with a parasite. However, very little is known about the types of B cells and Igs responding to bacterial infection in the teleost skin mucosa, as well as the inductive or effector role of the SALT in such responses. To address these questions, in this study, we analyzed the immune response of trout skin upon infection with one of the most widespread fish skin bacterial pathogens, Flavobacterium columnare This pathogen induced strong skin innate immune and inflammatory responses at the initial phases of infection. More critically, we found that the skin mucus of fish having survived the infection contained significant IgT- but not IgM- or IgD-specific titers against the bacteria. Moreover, we demonstrate the local proliferation and production of IgT+ B cells and specific IgT titers, respectively, within the SALT upon bacterial infection. Thus, our findings represent the first demonstration that IgT is the main Ig isotype induced by the skin mucosa upon bacterial infection and that, because of the large surface of the skin, its SALT probably represents a prominent IgT-inductive site in fish.

A Differential Immune Modulating Role of Vitamin D in Urinary Tract Infection.

ABSTRACT Vitamin D is known as an important modulator of numerous immune functions. We aimed to investigate the association of 25-hydroxyvitamin D [25(OH)D] with several humoral mediators of the immune system in the patients with urinary tract infection (UTI) caused by uropathogenic E. coli (UPEC). Serum levels of 25(OH)D, cytokines (interferon (IFN)-γ, interleukin (IL)–4, IL-6, IL–10, IL-17A, Tumor necrosis factor (TNF)–α, and transforming growth factor (TGF)–β, immunoglobulin (Ig) isotypes (IgG, IgM, and IgA), complement proteins (C3 and C4) with hemolytic activities (CH50 and AP50), and nitric oxide (NO) were evaluated in 65 patients, compared to 45 age- and sex-matched healthy controls. An insignificant decrease in 25(OH)D levels was observed in patients, compared to controls. In the patient group, elevated levels of IFN-γ, IL-17A, and IL-10 had a significant association with the serum levels of 25(OH)D, while the levels of TGF-β, IL-6, and TNF-α showed an insignificant association. The levels of IgG, C3, and NO also displayed such a statistically significant association with serum 25(OH)D levels. The AP50 levels which had significant difference were found to be not associated with serum 25(OH)D levels. Vitamin D might mediate a link between the innate and adaptive immune responses via the induction of Th1/Th17 polarization of cytokine responses and isotype regulation of antibody production, along with the maintenance of the capacity of the alternative complement pathway, in response to a UPEC infection. However, further studies are needed to validate the defined nature of the host immune response.

Interlaboratory Agreement of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Serologic Assays in the Expedited College of American Pathologists Proficiency Testing Program.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged, currently pandemic virus, and the etiologic agent of coronavirus disease 2019 (COVID-19). Clinical testing for antibodies to SARS-CoV-2 has rapidly become widespread, but data regarding the interlaboratory performance of these serologic assays are limited. To describe the development and initial results of the College of American Pathologists (CAP) SARS-CoV-2 Serology Survey. Members from the CAP Microbiology and Diagnostic Immunology and Flow Cytometry Committees formed a working group to support development of a new proficiency testing survey for anti-SARS-CoV-2 antibody assays. Supplemental questions in the survey assessed the state of SARS-CoV-2 serologic testing among participating laboratories as of July 2020. Results were analyzed for agreement by immunoglobulin (Ig) isotype tested, assay manufacturer, and methodology. A total of 4125 qualitative results were received from 1110 laboratories participating in the first survey. Qualitative agreement for assays measuring anti-SARS-CoV-2 total antibodies or IgG was greater than 90% for all 3 samples in the survey. Qualitative agreement for IgM and IgA for the negative sample was greater than 95%, but lacked consensus for the other 2 samples. These initial data suggest overall excellent agreement and comparable performance for most qualitative anti-SARS-CoV-2 IgG and total antibody assays across all participating clinical laboratories, regardless of specific target antigen or assay methodology.

Serum Hevylite® assay in the differential diagnosis of patients with high suspicion of AL Amyloidosis.

AL amyloidosis (AL) is a malignant form of plasma cell dyscrasia (PCD). It is insidious, and its end-organ damage can mimic that of common diseases. At diagnosis, routine tests for monoclonal protein are insufficient for the differential diagnosis. We hypothesized that Hevylite® (HLC) isotype patterns may help discriminate between AL and benign PCD states. Serum samples of patients with a high clinical suspicion of AL were prospectively tested for IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ concentrations and ratios using Hevylite® assays in a blinded manner. The results were correlated with the final diagnosis. Of the 99 samples analyzed, 46 were newly diagnosed AL, and the majority, 38 (82.6%), presented with suppression of at least one HLC isotype. Of the 53 benign PCD patients, 36 (67.9%) presented with elevation of at least one HLC isotype. By multivariate analysis, Hevylite® was the best independent test predictor of AL amyloidosis. HLC suppression had an odds ratio (OR) of 14.591, and elevation an OR of 10.149, and thus were significant variables in the diagnosis and exclusion of AL. Furthermore, patients with both HLC suppression, together with no elevation, had an OR of 316.69 to be diagnosed with AL rather than a benign PCD. Hevylite® HLC analysis for Ig isotypes patterns offers an effective non-invasive tool in the evaluation of patients with high suspicion of AL and may assist further explorative decisions for diagnosis.

C3 glomerulonephritis associated with monoclonal gammopathy: a retrospective case series study from a single institute in China

Objective To investigate the demographic and clinicopathological features and renal outcomes of Chinese patients with C3 glomerulonephritis in the setting of monoclonal gammopathy. Methods Patients with renal biopsy-proven C3 glomerulonephritis and detectable serum and/or urine monoclonal immunoglobulin from 2006 to 2018 in Peking University First Hospital were included, their clinical data, renal pathology type, treatment, and prognosis were collected and analyzed. Results Nineteen patients were enrolled, accounting for 24% of C3GN patients in the study period. The mean age of onset was 55 years old and the gender ratio was 4/15 (female/male). The mean eGFR at biopsy was 49.55 ± 29.81 ml/min/1.73m2. The prominent clinical manifestations included nephrotic syndrome (58%), anemia (68%), microscopic hematuria and leukocyturia (58%), and hypocomplementemia (13, 68%). The IgG was the most common isotype of monoclonal Ig on immunofixation electrophoresis. Kidney biopsies revealed a relatively prominent MPGN pattern. Only two patients had direct evidence of monocle immunoglobulins acting as C3GN pathogenic factors. Two patients had concurrent TMA-like renal injuries. The median renal survival was 12 and 15 months, respectively in patients receiving conservative therapy and immunosuppressant therapy, without statistical significance. The efficacy of clone-targeted therapy needed further investigation. Plasma exchange therapy only improved one patient’s renal outcome. Conclusions This is the first case series report of C3GN combined with monoclonal Ig in northern China. The renal prognosis of these patients is poor, and immunosuppressant therapies show no advantage over supportive therapy in renal prognosis, while the benefit of clone-targeted chemotherapy is still requiring investigation.

IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease.

Background and ObjectivesKawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined.MethodsIg levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease.ResultsCompared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs). Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022).ConclusionsHigh IgA levels in patients with KD are prognostic for the risk of CALs.

State of humoral immunity in lactating sows and suckling piglets

The state of humoral immunity in lactating sows and its formation in suckling piglets in the conditions of a pig-breeding complex were studied. In sows after farrow, a high content of total immunoglobulins, the main classes of IgG, IgM and IgA, the concentration of which decreased in a day, followed by an increase in serum as lactation continued was detected in the serum and colostrum. In piglets at birth, the content of total immunoglobulins and the main Ig isotypes was insignificant, and at the age of twenty-four hours, as a result of absorption of colostral immunoglobulins in the small intestine, their amount in the serum was the highest, followed by a decrease in the concentration of IgG and IgA until the end of the suckling period, and IgM - up to day 14 with a further increase in its content, indicating the formation of a primary immune response. It has been detected that the dominant class of immunoglobulins in the serum and colostrum of sows and the serum of piglets is IgG, and in milk - IgA. An increase in the level of medium-dispersed circulating immune complexes (C4%) and their relation to giant (C3%) CICs was revealed, associated with an increase of the antigenic load in sows in the second half of lactation as a result of immunization, in milk - with a decrease in the content of the main classes of immunoglobulins, and in piglets, due to this, with a decrease in passive immunity.