Elevated Levels Of Immunoglobulin Research Articles

Immunoglobulin E associated respiratory diseases: Part 2

Multiple pulmonary pathologies have been associated with elevated levels of Immunoglobulin E (IgE). Since its discovery in 1966, its role in multiple diseases has become clearer. This has allowed for the emergence of new medications that target IgE. In this review, we will summarize some of the most common pulmonary pathologies in which IgE has a role in their etiology.

Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo.

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.

1749-P: A Case Report of IgE-Mediated Insulin Allergy Successfully Managed with a Fixed Combination of Degludec and Liraglutide

Background: Insulin allergy is a rare condition that poses a great challenge particularly in diabetics who are insulin dependent. If feasible, switching to different antidiabetic agents or immunotherapy is the common approach, but the universal consensus on insulin allergy management in diabetics is lacking. Here we present a clinical case of a diabetic with allergy to insulin successfully managed with a combination of degludec and liraglutide. Case Report: A 51-year-old female patient with type 2 diabetes presented with poorly controlled glycaemia (HbA1c 8.6%) on dual oral antidiabetic treatment, metformin and sitagliptin. Due to pronounced fasting hyperglycaemia the NPH insulin before bedtime, but soon began to complain of urticariform skin lesions on insulin injection sites. Despite the adverse reaction the patient continued to up-titrate the insulin, but the effect on glycaemia was negligible. After switching to different NPH insulin manufacturer, to no avail, the insulin analogs detemir and glargin were introduced, respectively, but produced same adverse reaction. The elevated levels of specific IgE immunoglobulins to human insulin (2.58 klU/L) confirmed the allergy to insulin. Conversely, the novel insulin analog degludec yielded no skin reaction. The patient was then titrated to a fixed combination of degludec and GLP-1 receptor agonist liraglutide which provoked no allergic reaction and promptly improved glycemic control (HbA1c 6.7% 4 months after treatment commencement). Understandably, treatment with sitagliptin was stopped, whereas metformin was continued. Conclusion: The patient with confirmed IgE mediated allergy to insulin exhibited allergic reaction to all types of basal insulin but degludec. It can be assumed that the unique structure of degludec has different epitopes than other insulin analogues and therefore provides safe and combined with GLP-1 receptor agonist effective therapeutic approach to patient with allergy to insulin. Disclosure N. Gregoric: Other Relationship; Self; Lilly Diabetes, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. M. Ravnik Oblak: None. P. Kopac: Speaker's Bureau; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Shire.

Lower levels of leptin are associated with severity parameters in visceral leishmaniasis patients.

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, and if untreated may be fatal. It affects important organs of the immune system and is characterized by a specific immunosuppression, along with intense cellular activation and cytokine storm. Moreover, VL is now recognized as a systemic inflammatory response syndrome (SIRS), in which multiple cytokines and other pro-inflammatory molecules are released. The action of these inflammatory mediators may be considered risk factors for poor prognosis and death. Leptin, a hormone derived from adipose tissue, has been described with several immunoregulatory functions in vitro and in vivo Leishmania infection models, particularly for enhancing the macrophage microbicidal mechanisms. Considering that evaluation of immunologic parameters that may be associated with this clinical scenario may help to decrease VL lethality, we evaluated whether leptin is associated with VL pathogenesis. Thirty-one patients were recruited in the active phase of VL, of which 22 were followed up until one month after therapy (1mpt). Except for creatinine levels, all clinical parameters were altered in active VL patients, especially leucocyte counts and albumin and hemoglobin levels. Also, elevated levels of lipopolysaccharide (LPS), immunoglobulins (Ig)G1 and G3 anti-Leishmania and interleukins (IL)-6 and -10 were higher than in healthy individuals. In contrast, active VL patients presented diminished serum leptin levels and positive correlation with leukocytes counts and hemoglobin and albumin levels. After 1mpt, VL patients showed a significant increase in leptin levels, reaching values similar to healthy volunteers. As expected, only LPS levels remained elevated after 1mpt. These findings suggest that leptin levels are affected in Leishmania infection and the correlation with important parameters associated with the prognosis of VL points to the involvement of this molecule in VL immunopathogenesis. Additional studies are needed to evaluate the possibility of leptin as a prognostic marker of VL.

Schistosoma mansoni PCR+ -infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts.

Infections with Schistosoma mansoni remain a major health problem in the Sudan where endemic communities, such as those in Kassala and Khartoum states, continue to face severe social-economic difficulties. Our previous immunoepidemiological findings revealed different immune [cytokine and S. mansoni egg (SEA) antibody] profiles in individuals with active infections (eggs in stool n=110), individuals positive for S. mansoni via polymerase chain reaction (PCR) using sera (SmPCR+ n=63) and those uninfected (Sm uninf). As antibody responses to eggs and worms are known to change during infection, we have expanded the profiling further by determining levels of adult worm (SWA) antibodies and nine chemokines in the serum of each individual in the three different cohorts. With the exception of C-C motif chemokine ligand (CCL)2, all measured chemokines were significantly higher in SmPCR+ individuals when compared to the egg+ group and in addition they also presented elevated levels of SWA-specific immunoglobulin (Ig)G2. Multivariable regression analysis further revealed that infection per se was strongly linked to SWA-specific IgG3 levels and CCL5 was strongly associated with a SmPCR+ diagnostic state. In the absence of PCR diagnostics that recognize juvenile worms or schistosomulae motives, identifying schistosome-specific traits should provide better insights into current prevalence rates in endemic communities and, in doing so, take into consideration PCR+ non-egg+ individuals in current treatment programmes.

Elevation of immunoglobulin levels is associated with treatment failure in HIV-infected children in Vietnam.

BackgroundHIV-infected children suffer from higher levels of treatment failure compared to adults. Immunoactivation, including humoral immunoactivation reflected by increased immunoglobulin levels, is believed to occur early during HIV infection. Therefore, we wanted investigate alteration in immunoglobulin levels in association with treatment response in HIV-infected children.MethodsA nested case–control study was conducted using clinical data collected from 68 HIV-infected children enrolled at the National Hospital of Pediatrics, Vietnam.ResultsThe results showed that immunoglobulin levels, CD4 T-cell counts, CD4 T-cell percentage, and HIV load were significantly higher in the treatment-failure group than the treatment-success group at treatment initiation. IgG and IgA levels were negatively correlated with CD4 T-cell counts (P=0.049 and P<0.01, respectively) and positively correlated with HIV load (P=0.04 and P=0.02, respectively). In addition, IgG and IgA levels were independently associated with treatment response, analyzed by Cox regression analysis (HR 1.19 [P=0.049] and HR 1.69 [P<0.01], respectively).ConclusionElevation of IgA levels occurred early during HIV infection, and might have a prognostic role in treatment response.

Parasites and allergy: Observations from Africa.

SummaryPopulation studies from the African continent have observed a marked increase in the prevalence of allergy‐related diseases over the past few decades, but the cause of this rise is not fully understood. The most investigated potential risk factor has been the relationship between exposure to helminths and allergy‐related outcomes. Immunologically, parallels exist between responses to helminths and to allergens as both are associated with elevated levels of immunoglobulin E, increased numbers of T helper 2 cells and other immune cells. However, epidemiological studies from the African continent have found inconsistent results. In this review, observations from population studies carried out in Africa over the last decade that focus on the relationship between helminth infections and allergy‐related outcomes are examined. How these findings advance our understanding of the complex interactions between helminths and allergies at the population level is also explored as well as some of the underlying immune mechanisms involved. This knowledge is important for better diagnosis, treatment and prevention of allergy‐related diseases and has wider global significance.

Primary biliary cholangitis associated with drug-induced liver injury and alcoholic liver fibrosis

Rationale:Primary biliary cholangitis (PBC) is a liver autoimmune disease. If this disease is associated with other liver injury factors, both misdiagnosis and missed diagnosis will easily occur. Therefore, detailed disease history collection and related laboratory examination should be performed on patients with liver injury for unidentified causes. When necessary, liver biopsy should be performed to confirm the histopathological diagnosis.Patient concerns:The subject patient was a 63-year-old Chinese male with chronic liver injury who had a drinking history of about 30 years and drank 500 g daily on average and began to take health products and dietary supplements (multivitamins) since June 2014.Diagnoses:Drug-induced liver injury (DILI) and alcoholic fatty liver disease (AFLD) were initially considered because the patient had a history of using health products (HP) and dietary supplements (DS) and drinking alcohol. However, he was subsequently considered with PBC based on the findings of anti-mitochondrial antibody positivity and elevated immunoglobulin level. Obstructive jaundice and space-occupying lesion in the liver were excluded by imaging examinations. Liver biopsy was performed to confirm the reasons for liver injury. Histopathological examination was conducted, and the patient was diagnosed with PBC associated with DILI and alcoholic liver fibrosis.Interventions:Ursodeoxycholic acid, glycyrrhizic acid, and methylprednisolone (small dose) were used to treat the patient.Outcomes:After 2 months, the serum levels of ALT, AST, AKP, GGT, and globulin returned to normal. After 4 months, the patient showed liver injury once again (an increase in ALT, AST, AKP, GGT and GLB) caused by repaglinide administration due to hyperglycemia. Ursodeoxycholic acid and methylprednisolone replaced the repaglinide administration. After 3 weeks, the levels of ALT, AST, AKP, GGT, and GLB returned to normal again.Lessons:The correct knowledge on PBC and early-stage recognition and diagnosis should be emphasized. When other causes of the liver injury cannot be excluded, liver biopsy is suggested. Histopathological change can be used to further clarify the reasons for liver injury and the principal contradiction as well as to guide the theraputic regimen.

Acute Kidney Injury Following Methimazole Initiation: A Case Report

Objective: Nephritis has been rarely associated with methimazole, primarily in the development of nephrotic syndrome. We describe a case of acute kidney injury without evidence of nephrotic syndrome following methimazole initiation. Methods: We present the relevant history, laboratory data, and nuclear medicine data and review relevant documentation from the literature. Results: A 72-year-old male recently diagnosed with new-onset atrial fibrillation was found to have suppressed thyroid-stimulating hormone (TSH) levels; elevated free T3, T4, and thyroid-stimulating immunoglobulin (TSI) levels; and a nonnodular thyroid gland with normal iodine uptake. He was diagnosed with Graves’ disease and treated with propylthiouracil (PTU) for 5 years. When his poor compliance with PTU was impeding his antithyroid treatment, he was converted to methimazole. Within 1 month following methimazole initiation, his serum creatinine (SCr) had risen to 1.6× baseline in the absence of other contributing nephrotoxins. SCr returned to baseline within 2 weeks of methimazole discontinuation, and the patient was subsequently managed on PTU. Conclusion: Acute kidney injury with or without the presence of nephrotic syndrome may occur during treatment with methimazole. Renal function should be closely monitored after the initiation of methimazole to prevent progressive renal dysfunction.

N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.

Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells. Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared to Chinese hamster ovary cell-derived factor VIII. Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor. Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites. Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression. We did, however, observe increased levels of immunoglobulin M specific to baby hamster kidney-derived factor VIII in naïve hemophilia A mice. De-N-glycosylation enhanced immunoglobulin M binding, suggesting that N-glycan occupancy masks epitopes. Elevated levels of immunoglobulin M and immunoglobulin G specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased immunoglobulin G binding. Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of immunoglobulin M- and immunoglobulin G-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.

Genetic variants in RORA are associated with asthma and allergy markers in an admixed population

Asthma and allergy affect hundreds of millions of people from childhood to old age. In most of them, the inflammatory process of respiratory allergies involves the participation of type 2 cytokines, derived from T helper-2 (Th2)-cell, and Group 2 Innate Lymphoid (ILC2) Cells. An efficient memory Th2 cell response is dependent on IL-13 produced by ILC2s, causing allergic lung inflammation and elevated serum levels of immunoglobulin E. ILC2 cells are derived from common lymphoid progenitors and their growing depends on the transcription factor RORA. The aim of this work was to identify genetic variants in RORA associated with asthma phenotypes and allergy markers. Genomic DNA samples of 1246 individuals participating from Social Changes Asthma and Allergy in Latin America Program (SCAALA) have been genotyped using Illumina Human 2.5 Omni Beadchip. Logistics regressions have been performed to analyze the association among RORA variants and asthma, skin prick tests (SPT), specific IgE and type 2 cytokine production. Twelve single nucleotide variants (SNVs) were significantly associated with atopy (P < 0.01), in which four of them, rs10162630, rs17191519, rs17270243, and rs55796775 and their haplotypes were strongly and positively associated (P < 0.001). Furthermore, these variants increased the RORA gene expression in silico analysis. Other SNVs in RORA were associated with allergy markers, atopic and non-atopic asthma. Therefore, it is believed that variants in RORA gene may influence immunologic features of asthma and allergies and could be possible targets for future treatment of allergic diseases.

Dysbiosis of oral microbiota and its association with salivary immunological biomarkers in autoimmune liver disease.

The gut microbiota has recently been recognized to play a role in the pathogenesis of autoimmune liver disease (AILD), mainly primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This study aimed to analyze and compare the composition of the oral microbiota of 56 patients with AILD and 15 healthy controls (HCs) and to evaluate its association with salivary immunological biomarkers and gut microbiota. The subjects included 39 patients with PBC and 17 patients with AIH diagnosed at our hospital. The control population comprised 15 matched HCs. Salivary and fecal samples were collected for analysis of the microbiome by terminal restriction fragment length polymorphism of 16S rDNA. Correlations between immunological biomarkers measured by Bio-Plex assay (Bio-Rad) and the oral microbiomes of patients with PBC and AIH were assessed. Patients with AIH showed a significant increase in Veillonella with a concurrent decrease in Streptococcus in the oral microbiota compared with the HCs. Patients with PBC showed significant increases in Eubacterium and Veillonella and a significant decrease in Fusobacterium in the oral microbiota compared with the HCs. Immunological biomarker analysis showed elevated levels of inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-8) and immunoglobulin A in the saliva of patients with AILD. The relative abundance of Veillonella was positively correlated with the levels of IL-1β, IL-8 and immunoglobulin A in saliva and the relative abundance of Lactobacillales in feces. Dysbiosis of the oral microbiota is associated with inflammatory responses and reflects changes in the gut microbiota of patients with AILD. Dysbiosis may play an important role in the pathogenesis of AILD.

Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis.

Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal “healthy” tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress‐causing stimuli, may get activated to exhibit pro‐ or anti‐inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM‐regulated Diphtheria Toxin A expressing) strain with partial MΦ‐deficiency was crossed with the Scnn1b‐Tg mouse model of CB and the progenies were studied at 4–5 weeks of age. Compared with DTA− littermates, the DTA+ mice had ~50% reduction in bronchoalveolar lavage (BAL) MΦ, and the recovered MΦ were immature, phenotypically distinct, and functionally defective. DTA+/Scnn1b‐Tg mice exhibited a similar depletion of LysM+ MΦ offset by a significant increase in LysM‐ MΦ in the BAL. In DTA+/Scnn1b‐Tg mice, lung disease was more severe than in DTA−/Scnn1b‐Tg littermates, as indicated by an increased incidence of mucus plugging, mucous cells, airway inflammation, higher levels of cytokines/chemokines (KC, TNF‐α, MIP‐2, M‐CSF, IL‐5, and IL‐17), and worsened alveolar airspace enlargement. DTA+/Scnn1b‐Tg mice exhibited increased occurrence of lymphoid nodules, which was concomitant with elevated levels of immunoglobulins in BAL. Collectively, these data indicate that numerical deficiency of MΦ in stressed airspaces is responded via compensatory increase in the recruitment of immature MΦ and altered non‐MΦ effector cell‐centered responses, for example, mucus production and adaptive immune defense. Overall, these data identify dynamic roles of MΦ in moderating, rather than exacerbating, the severity of lung disease in a model of CB.

A case of intra-operative anaphylactic shock in hepatic hydatidosis with inadequate chemotherapy and proximity to hepatic vessels

Incidence of intraoperative Hydatid anaphylaxis is 0.2-3.3% Reporting of such rare cases is crucial for future reference and study. 52 years old lady presented with hepatic hydatidosis. Computed Tomography showed 2 cystic lesions; one in segment 6, 7 in proximity to right hepatic vein; multiseptated cyst with multiple daughter cysts in segment 4 adjoining the middle hepatic vein with intracystic vessel. No rupture seen. Preoperatively she was prescribed Albendazole 400mg twice-daily for 3months. She was given Hydrocortisone before surgery. 10% povidone iodine mops to prevent intraperitoneal spillage and hypertonic saline used to flush the cyst. One hour after anesthesia when the Segment IV cyst close to middle hepatic vein was punctured she had anaphylactic shock, resuscitated. Marsupialization of both the cysts with omentoplasty and intracystic drains done. She recovered well and discharged with Albendazole for 1 month. Growing cyst produces complex echinococcal antigens, increased cellular immune response, Th2 balanced with Th1; elevated immunoglobulin levels. In dead cysts Th2 responses drop rapidly. Albendazole 10mg/kg for 3 months causes good cyst wall degeneration, less viability of protoscoleces and cyst, less echinococcal antigen production. After the surgery we found that she had stopped albendazole in the preoperative period, which she did not reveal pre-operatively fearing delay in surgery. Inadequate albendazole, close proximity of cysts to vascular structures with high intracystic pressure would have predisposed to develop anaphylactic shock during cyst handling. Preoperative Albendazole can reduce anaphylaxis, morbidity and mortality due to hydatid, making hydatid surgery safer.

Altered immunoglobulins (A and G) in Ghanaian patients with type 2 diabetes.

Objectives:Elevated immunoglobulin levels have been strongly linked to the development and progression of inflammatory disorders such as type 2 diabetes and obesity. This study aimed to evaluate circulating immunoglobulin levels and to identify other metabolic factors that influence humoral immune response among Ghanaian subjects with type 2 diabetes.Methods:A comparative cross-sectional study conducted at the National Diabetes Management and Research Center, Accra. Eighty persons with type 2 diabetes were age-matched with 78 controls. Immunoglobulin A, immunoglobulin G and immunoglobulin M; interleukin 6; fasting blood glucose; glycated hemoglobin; and lipid parameter concentrations were measured. Blood pressure, anthropometry and body composition indices were also assessed.Results:Median immunoglobulin A and immunoglobulin G (g/L) levels were higher in the case group compared with controls (0.89 vs 0.74, p = 0.043; 7.58 vs 7.29, p < 0.001). Immunoglobulin G, immunoglobulin A and interleukin 6 levels in the case cohort, respectively, associated weakly with fasting blood glucose (r = 0.252, p = 0.001; r = 0.170, p = 0.031; r = 0.296, p = 0.001). There were positive correlations within the control group for immunoglobulin A versus interleukin 6 (r = 0.366, p = 0.001) and within the case group for glycated hemoglobin versus interleukin 6 (r = 0.190, p = 0.020).Conclusion:Our data suggest that humoral immune response is altered in subjects with type 2 diabetes and that serum immunoglobulin levels could serve as useful biomarkers in the investigation and management of diabetes mellitus.

Associations between self-rated health, sickness behaviour and inflammatory markers in primary care patients with allergic asthma: a longitudinal study

Allergic asthma is a chronic inflammatory disorder associated with elevated levels of immunoglobulin E (IgE), serum eosinophilic cationic protein (S-ECP), plasma eosinophil-derived neurotoxin (P-EDN) and fraction of exhaled nitric oxide (FENO). Poor self-rated health and sickness behaviour has repeatedly been associated with inflammatory markers, but the nature of this relationship in chronic inflammatory disease is not known. Likewise, such findings largely rely on cross-sectional investigations. Self-rated health (How would you rate your general state of health?), sickness behaviour (mean rating of satisfaction with energy, sleep, fitness, appetite and memory), IgE, S-ECP, P-EDN, and FENO were assessed in 181 non-smoking primary care patients with asthma in a 1-year longitudinal study. Associations between repeated measurements were calculated using mixed regression models and Spearman’s correlations for change scores. Poor self-rated health was associated with high levels of seasonal IgE (p = 0.05) and food IgE (p = 0.04), but not total IgE or inflammatory markers. An increase over 1 year in perennial IgE was associated with a worsening of self-rated health (ρ = 0.16, p = 0.04). Poor self-rated health was associated with more pronounced sickness behaviour (p < 0.001), and a worsening in sickness behaviour was associated with a worsening of self-rated health over time (ρ = 0.21, p = 0.007). The study corroborates the importance of sickness behaviour as a determinant of self-rated health by showing that these factors co-vary over a 1-year period in a group of patients with allergic asthma. The importance of specific IgE for perceived health in primary care patients with mild to moderate asthma needs further investigation.

T-bet+CD11c+ B cells are critical for antichromatin immunoglobulin G production in the development of lupus

BackgroundA hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c+ B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+ B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c+ B cells in the pathogenesis of lupus in cGVHD mice.MethodscGVHD was induced by an intraperitoneal injection of 5 × 107 Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants.ResultsThe percentage and absolute number of CD11c+ B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c+ plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet+CD11c+ B cells increased in lupus patients and positively correlated with serum antichromatin levels.ConclusionT-bet+CD11c+ B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet+CD11c+ B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.

Correlation between elevated platelet count and immunoglobulin levels in the early convalescent stage of Kawasaki disease.

Kawasaki disease (KD) may be an acute systemic immune-mediated disease which occurs after infection of unknown KD pathogen(s). The aim of this study is to evaluate the changes in platelet count and immunoglobulin (Ig) levels (IgG, IgM, IgA, and IgE) during hospitalization.Forty-three patients with complete KD who received intravenous Ig at 2 g/kg were enrolled in South Korea. The platelet count and Ig levels of the patients were examined twice at presentation and around discharge (mean 6.2 ± 2.4 days apart) and the relationships between platelet level and Ig levels were evaluated.The mean patient age was 31 ± 18 months; 28 patients were male and 15 were female. The values of all parameters measured, with the exception of IgE, were significantly increased at the second examination compared with their values at presentation. These values gradually increased over time after fever onset, over periods ranging from 2 to 16 days. The extent by which platelet levels increased over these 2 time points was correlated with the extents by which IgG (P < .01), IgM (P < .01), and IgA levels (P = .01) increased.Both the platelet count and the Ig (IgG, IgM, and IgA) levels increased with a correlation each other during the early convalescent stage of KD. This finding suggests that all Ig subtypes except IgE and platelets may be involved in the recovery from KD and that the extent of increased parameters may reflect the degree of systemic inflammation in acute KD.

TAFRO syndrome: New subtype of idiopathic multicentric Castleman disease.

Castleman disease (CD) describes a group of three rare and poorly understood lymphoproliferative disorders that have heterogeneous clinical symptoms and common lymph node histopathological features. Unicentric CD (UCD) involves a single region of enlarged nodes. Multicentric CD (MCD) involves multiple regions of enlarged lymph nodes, constitutional symptoms, and organ dysfunction due to a cytokine storm often including interleukin 6. MCD is further divided into Human Herpes Virus-8 (HHV-8)-associated MCD, which occurs in immunocompromised individuals, and HHV-8-negative/idiopathic MCD (iMCD). Recently, iMCD has been further sub-divided into patients with TAFRO syndrome, which involves thrombocytopenia (T), anasarca (A), fevers (F), reticulin myelofibrosis (R), organomegaly (O), and normal or only slightly elevated immunoglobulin levels, and those who do not have TAFRO syndrome. Non-TAFRO iMCD patients typically have thrombocytosis, less severe fluid accumulation, and hypergammaglobulinemia. iMCD patients with TAFRO syndrome may have a worse prognosis, but more research is needed.

Elevated serum levels of immunoglobulin A correlate with the possibility of readmission in patients with microscopic polyangiitis.

The evidence for the short-term prognosis of patients with microscopic polyangiitis (MPA) is weak, and the objective of this study was to analyze the clinical features of the disease and evaluate the risk factors for readmission in patients with MPA. Fifty-seven patients with MPA were recruited into this study. The clinical data of these MPA patients were collected. Clinical manifestations, laboratory results, and imaging results were analyzed. Patients who were readmitted to our hospital within 6 months after their first diagnosis and treatment of MPA were defined as the readmission group; the remaining patients were defined as the control group. Respiratory symptoms, including cough, dyspnea (87.72%), and hemoptysis (3.51%), seemed to be the initial symptoms in many patients with MPA. Systemic symptoms included fever (71.93%), hearing loss (12.28%), vision loss (3.51%), and joint involvement (5.27%). The D-dimer levels of 43 patients (75.44%) were >500 ng/dL, and only three of these patients had venous thrombosis. Age and immunoglobulin A (IgA) were the risk factors for readmission in patients with MPA, with odds ratios (ORs) of 1.162 [95% confidence interval (CI): 1.025-1.317, P=0.019] and 1.010 (95% CI: 1.001-1.018, P=0.028). The days of hospitalization and the a2-globulin level were protective factors with ORs of 0.849 (95% CI: 0.725-0.993 P=0.041) and 0.789 (95% CI: 0.64-0.971, P=0.025), respectively. IgA levels were positively correlated with the number of hospitalizations, with a correlation coefficient of 0.428 (P=0.002). Receiver operating characteristic curve analysis showed that the possibility of readmission increases when the serum levels of IgA were >217.5 mg/dL. The level of serum IgA is a risk factor for the readmission of patients with MPA, and correlated with the number of hospitalizations in these patients.