Low IgG Levels Research Articles

Colostrum source and passive immunity transfer in dairy bull calves

Colostrum is essential for good neonate health; however, it is not known whether different calves absorb the nutrients from colostrum equally well. In this study, the absorption of protein, IgG, and γ-glutamyl transferase was compared in newborn dairy bull calves for 1 wk after feeding colostrum from different sources. Thirty-five Holstein-Friesian bull calves were randomly allocated into 3 groups and fed colostrum within 4 h after birth. Group A calves (n = 12) were bottle fed colostrum from their own dam for 3 d. Colostrum from these group A cows was also used as foster cow colostrum for the group B calves (n = 12), such that each group A and B calf pair received identical colostrum from each milking of the respective group A dam (10% of birth weight per day). The group C calves (n = 11) were fed 1 bottle (2 L) of pooled colostrum and transition milk (referred to as pooled colostrum), as was the standard practice on the dairy farm. The pooled colostrum was collected from the other dairy cows on the farm 0 to 4 d postpartum and stored at 4°C for less than 12 h. Blood was sampled from calves before the first feeding and at 1, 2, 3, and 7 d after birth. Levels of total solids, total protein, and IgG were higher in the dam colostrum than in the pooled colostrum. At birth, there were no differences between the calf groups for any measurements, and all calves had very low IgG levels. After receiving colostrum, the glucose, plasma γ-glutamyl transferase, serum total protein, and IgG concentrations increased significantly in all calves. There were no differences in any blood measurements at any time point between the pairs of group A and group B calves that received colostrum from the same cow except for the IgG concentration 2 d after birth. However, the group A calves had a higher total serum protein level and IgG concentration than the group C calves for all the time points after the first feeding. The group B calves had a higher IgG concentration than the group C calves on d 1, 2, and 7 after birth. Compared with groups A and B, there was no difference in the proportion of calves in group C that failed to have passive immunity transferred adequately based on the IgG threshold (<10 g/L). Thus, the calves receiving identical colostrum from the same cow had the same levels of IgG, and even the pooled colostrum provided sufficient transfer of IgG as the calves were fed within 4 h after birth.

Risk factors for SARS-CoV-2 re-positivity in COVID-19 patients after discharge

ObjectiveRe-positivity of SARS-CoV-2 in discharged COVID-19 patients have been reported; however, early risk factors for SARS-CoV-2 re-positivity evaluation are limited. MethodsThis is a prospective study, a total of 145 COVID-19 patients were treated and all discharged according to the guideline criteria by Mar 11th 2020. After discharge, clinical visits and viral RT-PCR tests by the second and fourth week follow-up were carried-out. Patient demographic and clinical characteristics and laboratory data on admission and discharge were retrieved, and predictive factors for SARS-CoV-2 re-positivity were analyzed. Results13 out of 145 (9.0%) COVID-19 patients were confirmed re-positivity of SARS-CoV-2 by RT-PCR test. The median interval between disease onset to recurrence was 38 days. SARS-CoV-2 re-positive cases were of significantly longer virus shedding duration, notably higher body temperature, heart rate and lower TNF-α and IgG levels on admission. Covariate logistic regression analysis revealed virus shedding duration and IgG levels are independent risk factors for SARS-CoV-2 return positive after discharge. ConclusionLonger viral shedding duration and lower IgG levels are risk factors for re-positivity of SARS-CoV-2 for discharged COVID-19 patients.

Autoimmune Hepatitis in a Patient With Common Variable Immunodeficiency

ABSTRACTCommon variable immunodeficiency (CVID) is characterized by defective immunoglobulin synthesis because of impaired B-cell function. Liver abnormalities including autoimmune hepatitis (AIH) have been described in up to 10% of patients. We report a 27-year-old woman with CVID who presented with liver dysfunction secondary to AIH. AIH is both uncommon and challenging diagnostically in patients with CVID because they have low IgG levels and often have low or undetectable autoantibody levels. Liver biopsy and response to therapy play an important role in establishing the diagnosis. Corticosteroids are the mainstay of therapy, with or without immune modulators.

Clinical features and antibody response of patients from a COVID-19 treatment hospital in Wuhan, China.

Coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic.A total of 1578 patients admitted into a newly built hospital specialized for COVID-19 treatment in Wuhan, China, were enrolled. Clinical features and the levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)M and IgG were analyzed.In total, 1532 patients (97.2%) were identified as laboratory-confirmed cases. Seventy-seven patients were identified as asymptomatic carriers (n = 64) or SARS-CoV-2 RNA positive before symptom onset (n = 13). The positive rates of SARS-CoV-2 IgM and IgG were 80.4% and 96.8%, respectively. The median of IgM and IgG titers were 37.0A U/ml (interquartile range [IQR]:13.4-81.1 AU/ml) and 156.9 AU/ml (IQR: 102.8-183.3 AU/ml), respectively. The IgM and IgG levels of asymptomatic patients (median titers, 8.3 AU/ml and 100.3 AU/ml) were much lower than those in symptomatic patients (median titers, 38.0 AU/ml and 158.2 AU/ml). A much lower IgG level was observed in critically ill patients 42-60 days after symptom onset. There were 153 patients with viral RNA shedding after IgG detection. These patients had a higher proportion of critical illness during hospitalization (p < .001) and a longer hospital stay (p < .001) compared to patients with viral clearance after IgG detection. Coronary heart disease (odds ratio [OR], 1.89 [95% confidence interval [CI], 1.11-3.24]; p = .020), and intensive care unitadmission (OR, 2.47 [95% CI, 1.31-4.66];p = .005) were independent risk factors associated with viral RNA shedding after IgG detection.Symptomatic patients produced more antibodies than asymptomatic patients. The patients who had SARS-CoV-2 RNA shedding after developing IgG were more likely to be sicker patients.

Impact of Coinfection with Schistosoma mansoni on the Antibody Response to Helicobacter pylori.

In many tropical areas, the coinfection of Schistosoma spp. and other pathogens is frequent. The impact of schistosomiasis on other infections has been demonstrated for several organisms. Infection with the widely spread bacterium, Helicobacter pylori, has been linked to ulcers and tumors of the digestive system with the humoral immune response playing possible modulatory roles. The present study investigated the impact of patent S. mansoni infection on the antibody response to H. pylori. A total of 100 participants from a schistosomiasis endemic area in Egypt were enrolled in the study. Based on the detection of S. mansoni eggs and H. pylori coproantigen in fecal samples, they were equally divided into four groups: schistosomiasis, concomitant S. mansoni and H. pylori infection, H. pylori infection alone, and healthy controls. Anti-H. pylori IgG and IgA were determined in serum samples using ELISA. A significantly lower IgA seropositivity rate and significantly lower IgG levels were found in patients with concomitant schistosomiasis (Gp2) compared to those infected only with H. pylori (Gp1). Concomitant S. mansoni infection with light to moderate intensity alters serological responses to H. pylori. In schistosomiasis endemic areas, the routine examination for H. pylori infection should, therefore, rely on coproantigen level rather than antibody levels. Further studies should investigate histopathological changes and other immunological parameters in coinfection.

The Immunogenicity of Capsid-Like Particle Vaccines in Combination with Different Adjuvants Using Different Routes of Administration.

Capsid-like particle (CLP) displays can be used to enhance the immunogenicity of vaccine antigens, but a better understanding of how CLP vaccines are best formulated and delivered is needed. This study compared the humoral immune responses in mice elicited against two different vaccine antigens (a bacterial protein and a viral peptide) delivered on an AP205 CLP platform using six different adjuvant formulations. In comparison to antibody responses obtained after immunization with the unadjuvanted CLP vaccine, three of the adjuvant systems (neutral liposomes/monophosphoryl lipid A/quillaja saponaria 21, squalene-in-water emulsion, and monophosphoryl lipid A) caused significantly increased antibody levels, whereas formulation with the three other adjuvants (aluminum hydroxide, cationic liposomes, and cationic microparticles) resulted in similar or even decreased antibody responses. When delivering the soluble bacterial protein in a squalene-in-water emulsion, 4-log lower IgG levels were obtained compared to when the protein was delivered on CLPs without the adjuvant. The AP205 CLP platform promoted induction of both IgG1 and IgG2 subclasses, which could be skewed towards a higher production of IgG1 (aluminum hydroxide). Compared to other routes, intramuscular administration elicited the highest IgG levels. These results indicate that the effect of the external adjuvant does not always synergize with the adjuvant effect of the CLP display, which underscores the need for empirical testing of different extrinsic adjuvants.

Clinical characteristics and potential factors for recurrence of positive SARS-CoV-2 RNA in convalescent patients: a retrospective cohort study.

BackgroundThe recurrence of positive SARS-CoV-2 RT-PCR is frequently found in discharged COVID-19 patients but its clinical significance remains unclear. The potential cause, clinical characteristics and infectiousness of the recurrent positive RT-PCR patients need to be answered.MethodsA single-centered, retrospective study of 51 discharged COVID-19 patients was carried out at a designated hospital for COVID-19. The demographic data, clinical records and laboratory findings of 25 patients with recurrent positive RT-PCR from hospitalization to follow-up were collected and compared to 26 patients with negative RT-PCR discharged regularly during the same period. Discharged patients’ family members and close contacts were also interviewed by telephone to evaluate patients’ potential infectiousness.ResultsThe titer of both IgG and IgM antibodies was significantly lower (p = 0.027, p = 0.011) in patients with recurrent positive RT-PCR. Median duration of viral shedding significantly prolonged in patients with recurrent positive RT-PCR (36.0 days vs 9.0 days, p = 0.000). There was no significant difference in demographic features, clinical features, lymphocyte subsets count and inflammatory cytokines levels between the two groups of patients. No fatal case was noted in two groups. As of the last day of follow-up, none of the discharged patients’ family members or close contact developed any symptoms of COVID-19.ConclusionsPatients with low levels of IgG and IgM are more likely to have recurrent positive SARS-CoV-2 RT-PCR results and lead to a prolonged viral shedding. The recurrent positive of SARS-CoV-2 RT-PCR may not indicate the recurrence or aggravation of COVID-19. The detection of SARS-CoV-2 by RT-PCR in the patients recovered from COVID-19 is not necessarily correlated with the ability of transmission.

Neuraminidase Inhibitor Zanamivir Ameliorates Collagen-Induced Arthritis.

Altered sialylation patterns play a role in chronic autoimmune diseases such as rheumatoid arthritis (RA). Recent studies have shown the pro-inflammatory activities of immunoglobulins (Igs) with desialylated sugar moieties. The role of neuraminidases (NEUs), enzymes which are responsible for the cleavage of terminal sialic acids (SA) from sialoglycoconjugates, is not fully understood in RA. We investigated the impact of zanamivir, an inhibitor of the influenza virus neuraminidase, and mammalian NEU2/3 on clinical outcomes in experimental arthritides studies. The severity of arthritis was monitored and IgG titers were measured by ELISA. (2,6)-linked SA was determined on IgG by ELISA and on cell surfaces by flow cytometry. Zanamivir at a dose of 100 mg/kg (zana-100) significantly ameliorated collagen-induced arthritis (CIA), whereas zana-100 was ineffective in serum transfer-induced arthritis. Systemic zana-100 treatment reduced the number of splenic CD138+/TACI+ plasma cells and CD19+ B cells, which was associated with lower IgG levels and an increased sialylation status of IgG compared to controls. Our data reveal the contribution of NEU2/3 in CIA. Zanamivir down-modulated the T and B cell-dependent humoral immune response and induced an anti-inflammatory milieu by inhibiting sialic acid degradation. We suggest that neuraminidases might represent a promising therapeutic target for RA and possibly also for other antibody-mediated autoimmune diseases.

Иммунологические показатели как прогностические маркеры исхода суставсберегающих операций у детей с ишемическими деформациями проксимального отдела бедра (предварительные результаты)

Objective Assess the immune status of children with ischemic deformity of the proximal femur taking into account the treatment outcome. Material and methods Preoperative assessment of the immune status was performed for 16 adolescents with ischemic deformity of the proximal femur. Patients' age was 14.4 ± 0.45 years. Immunological parameters of 12 adolescents with satisfactory (group I) and 4 patients with poor (group II) anatomical and functional outcome of surgical treatment were compared. Peripheral blood lymphocyte typing was produced with laser cytometry assay, and IgA, IgM, IgG, IgE, IL-18, IFNγ and circulating immune complexes were quantified with enzyme-linked immunoassay. Results Сomparative analysis of preoperative immunological parameters showed statistically significant decline of Т-helper cells (СD3+СD4+), high levels of activated СD3+CD25 and СD3+HLADR T lymphocytes, low levels of activated NК cells (СD8dimCD38+) and IFNγ in group II. Humoral immune parameters indicated to low levels of IgA, IgM, IgG and higher levels of circulating immune complexes in group II relative to group I. Conclusion Preliminary data obtained suggest that cellular and humoral immune deficiency can be associated with unfavorable outcome of joint preservation procedure. Such immunological parameters as T lymphocytes subpopulation, immunoglobulins, circulating immune complexes and IFNγ can be used as significant prognostic factors for preoperative planning and postoperative rehabilitation of adolescents with ischemic deformity of the proximal femur.

Prophylactic Antibiotics Versus Immunoglobulin Replacement in Specific Antibody Deficiency

J Hajjar, AL Nguyen, G Constantine. J Clin Immunol. 2020;40:158–164 To compare treatment outcomes in patients with specific antibody deficiency (SAD) who were treated with immunoglobulin replacement therapy (IGRT) and/or prophylactic antibiotics (PA). This study included 65 patients with SAD (mean age 18, range 2–71 years old) who were treated with IGRT and/or PA at two tertiary care centers in the United States. This was a retrospective chart review that evaluated clinical characteristics, laboratory findings, treatment patterns and clinical outcomes of patients with SAD who were treated with IGRT and/or PA. All patients were followed …

The immune gene expression induced by Cooperia punctata in naturally infected calves with resistance and susceptible phenotype traits

The analysis of the immune gene expression was performed in Zebu × Holstein calves with resistant and susceptible phenotypes naturally infected with Cooperia punctata. Fourteen calves of 4 months old were grazed for 11 weeks under a tropical climate. The parasitic infection showed an average epg value of 1055 ± 1155 and an IgG optical density of 0.814 ± 0.0.037 with statistic differences among the different weeks (p < 0.05), and a pcv value of 24 ± 2.0 % (p > 0.05). High variation in epg value was observed, between 7 ± 7.14 and 4657 ± 1886, and, based on these differences; the infected hosts were classified as five resistant calves with epg ≤ 200 and nine susceptible calves with epg ≥ 300. Moreover, IgG levels displayed statistical differences between resistance and susceptible calves to C. punctata infection. The immune gene expression was analysed in three resistant and susceptible calves, respectively. Nine cytokine genes and the FCεR1A receptor were analysed at the 3rd and 11th weeks post-infection. In the first period upregulation was found, from 2.19- to 9.45-fold, (p < 0.05) for IL-2, -5, - 6, -10, TGF-β and FCεR1A in the resistant group; the expression was decreased at the 11th week with low level of IgG. In contrast, downregulation for susceptible calves was found for nine immune genes and upregulation for INF-γ in both periods together with increased IgG levels. In conclusion, immune gene expression was regulated at the begging infection of C. punctata in resistant grazing calves. In contrast, suppression of important genes was involved in calves susceptible to C. punctata.

Autoimmune Cytopenias in Nonmalignant Lymphoproliferative Disorders: Thinking Beyond ALPS(Autoimmune Lymphoproliferative Syndrome)

The ALPS Clinic at NIH has studied autoimmune lymphoproliferative disorders for over 30 years elucidating the genetic underpinnings and natural history of Autoimmune Lymphoproliferative Syndrome (ALPS) due to FAS gene defects (Blood 2014). Over the years, we continue to receive and work-up numerous referrals for diseases that masquerade like ALPS-FAS, presenting with multi-lineage cytopenias due to autoimmune peripheral destruction and splenic sequestration in the setting of non-malignant lymphoproliferation. In a review of 259 cases evaluated by our team, there were 150 ALPS-FAS, 54 Activated PI3K-delta Syndrome (APDS), 31 CTLA-4 Haploinsufficiency (CTLA4), 7 LRBA deficiency (LRBA), and 17 MAGT-1 deficiency (XMEN) patients. Non-malignant lymphadenopathy and splenomegaly occurred on average in 83% and 71% of all patients, respectively. Anemia, thrombocytopenia, and neutropenia were seen in 65%, 58%, and 46%, respectively. Thus, autoimmune cytopenias in the setting of non-malignant lymphoproliferation in themselves are not adequate to rule in or rule out a presumptive diagnosis of ALPS-FAS. Timely and accurate genetic diagnosis of ALPS-like conditions will improve the morbidity and mortality associated with these disease processes. Rapamycin, an m-TOR inhibitor provides salutary benefits for many of these conditions by restoring the TREG function and reversing immune-dysregulation. For example, in addition to lymphadenopathy and splenomegaly associated with an increased risk of malignant lymphoma like ALPS-FAS patients, APDS patients usually present with recurrent sinopulmonary and ear infections. Their serum IgM tends to be elevated with low IgG levels. Unlike for ALPS-FAS patients, a potential targeted treatment for APDS exists: Leniolisib, a targeted PI3Kinase p-110 delta inhibitor is currently undergoing clinical trials (Blood 2016). CTLA-4 is critical for T-cell activation and immune check-point regulation by tempering regulatory T cell function. Patients affected by CTLA4 and LRBA variants present with symptoms of lymphocytic infiltration of the bone marrow (often leading to hypoplastic anemia), gut (colitis, bowel obstruction), lungs (bronchiectasis, restrictive airway disease), and central nervous system (seizures and neurological deficits due to brain and spinal cord lesions). They also tend to have B cell lymphopenia, low IgG and IgM levels. CTLA4 and LRBA patients share pathophysiology as well as clinical phenotype because LRBA gene regulates intracellular lysosomal trafficking and recycling of CTLA-4 protein. Hence CTLA-4 haploinsufficiency or LRBA deficiency renders both patient types CTLA-4 deficient. This can be directly addressed with abatacept infusions, a CTLA-4 hybridized immunoglobulin given as a combination immunosuppressive therapy with rapamycin. Abatacept replaces the CTLA-4 molecule and reverses some of the immune dysregulation and thus morbidity associated with both CTLA4 and LRBA deficiency. Like APDS patients, XMEN patients are also prone to recurrent ear and sinopulmonary infection, but key differentiating features of this X-linked disorder are that only males are affected, these patients are unable to clear Epstein-Barr virus (EBV) once exposed, and they have a propensity to develop EBV-driven lymphomas. These patients also usually have a strong family history of multiple lymphomas in males. Even though a targeted treatment does not yet exist, steroid-sparing measures such as rituximab, rapamycin and mycophenolate mofetil are the first-line treatments often used in managing their refractory autoimmune cytopenias. Hence accurate early genetic diagnosis is key to accessing the appropriate treatment, thus decreasing the morbidity and mortality associated with these childhood onset ALPS-like rare inherited disorders (table). Table Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Rapamycin, Abatacept, Mycophenolate Mofetil.

Questioning Cause and Effect: Children with Severe Asthma Exhibit High Levels of Inflammatory Biomarkers Including Beta-Hexosaminidase, but Low Levels of Vitamin A and Immunoglobulins.

Asthma affects over 8% of the pediatric population in the United States, and Memphis, Tennessee has been labeled an asthma capital. Plasma samples were analyzed for biomarker profiles from 95 children with severe asthma and 47 age-matched, hospitalized nonasthmatic controls at Le Bonheur Children’s Hospital in Memphis, where over 4000 asthmatics are cared for annually. Asthmatics exhibited significantly higher levels of periostin, surfactant protein D, receptor for advanced glycation end products and β-hexosaminidase compared to controls. Children with severe asthma had lower levels of IgG1, IgG2 and IgA, and higher levels of IgE compared to controls, and approximately half of asthmatics exhibited IgG1 levels that were below age-specific norms. Vitamin A levels, measured by the surrogate retinol-binding protein, were insufficient or deficient in most asthmatic children, and correlated positively with IgG1. Which came first, asthma status or low levels of vitamin A and immunoglobulins? It is likely that inflammatory disease and immunosuppressive drugs contributed to a reduction in vitamin A and immunoglobulin levels. However, a nonmutually exclusive hypothesis is that low dietary vitamin A caused reductions in immune function and rendered children vulnerable to respiratory disease and consequent asthma pathogenesis. Continued attention to nutrition in combination with the biomarker profile is recommended to prevent and treat asthma in vulnerable children.

S3048 A Secondary Hypogammaglobinemia in a Patient With Eosinophilic Gastritis

INTRODUCTION: Eosinophilic gastroenteritis (EGE) is a rare inflammatory disorder characterized by eosinophilic infiltration of the gastrointestinal (GI) tract. The pathogenesis remains largely unknown but several studies have suggested involvement of IL-5+ Th2 cells and cytokines IL-3, IL-5, and granulocyte macrophage-colony stimulating factor. EGE usually manifests with non-specific GI symptoms as well as, in some cases, severe iron-deficiency anemia. A secondary hypogammaglobinemia is not an established complication of EGE, but can be a consequence of iron-deficiency anemia. We present an active duty patient with EGE, found to have severe iron-deficiency anemia with low IgG level and loss of immune titer to MMR, Rubeola and Varicella. CASE DESCRIPTION/METHODS: A 25-year-old active duty soldier presented to emergency room with dyspnea and fatigue and was incidentally found to be severely anemic (Hemoglobin: 6.3g/dL, MCV: 62.7fL, and Ferritin: 2.86ng/mL) with absolute eosinophil (Abs Eo) of 1.0 × 10(9)/L. She received blood transfusion and was started on enteral iron therapy, as well as, work-up for eosinophilia to include malignancy, infection, and autoimmune/vasculitis etiologies. At 6 month follow-up, hemoglobin normalized to 15.2g/dL but eosinophilia persisted, reaching as high as 2.44 × 10(9)/L. As part of the work-up, immunoglobin was obtained which showed low IgG (328mg/dL), but normal levels of IgA, IgM, and IgE. She was also noted to have lost titer to MMR, Rubeola, and Varicella (though having had previously received all appropriate vaccinations in 2015 for military service). During primary immunodeficiency work-up, she was placed on inhaled fluticasone by pulmonology for presumed diagnosis of eosinophilic asthma (PFTs were normal). Patient clinically improved with subsequent lab showing improvement in IgG level and down-trending eosinophil counts. She was re-vaccinated and developed appropriate level of immune titers to all the vaccines. DISCUSSION: EGE is a rare inflammatory disorder of GI tract with non-specific GI symptoms. While secondary hypogammaglobinemia is not an established complication of EGE, our case raises the question of whether patients diagnosed with EoE or EGE should additionally be screened for secondary hypogammaglobinemia and/or associated loss of immune titers to vaccines.

B7-H4 Inhibits the Development of Primary Sjögren's Syndrome by Regulating Treg Differentiation in NOD/Ltj Mice.

Background This study is aimed at exploring the role of B7-H4 in the pathogenesis of primary Sjögren's syndrome (pSS) in NOD/Ltj mouse. Methods B7-H4 expression in salivary glands was examined by IHC, and lymphocyte infiltration was showed by H&E. Next, anti-B7-H4 mAb or immunoglobulin isotype was injected into NOD/Ltj mice. Cytokine levels were measured by quantitative RT-PCR, and immunoglobulins were measured by ELISA. T cell subsets were analyzed by flow cytometry. Last, we treated NOD/Ltj mice with B7-H4Ig and control Ig. CD4+Foxp3+ T cells were assessed by immunohistochemistry. Two-tailed Student's t-tests were used to detect the statistical difference in various measures between the two groups. Results B7-H4 expression was remarkably reduced in salivary glands of NOD/Ltj mice at 15 weeks compared with the NOD/Ltj mice at 8 weeks. Anti-B7-H4 mAb treatment increased lymphocyte infiltration in salivary glands. Inflammatory cytokines including IL-12, IL-18, IL-1α, TNF-α, IFN-α, and BAFF were upregulated markedly in anti-B7-H4 mAb-treated mice compared to IgG isotype-treated mice. Flow cytometry analysis showed that anti-B7-H4 mAb-treated mice had lower levels of CD4+Foxp3+/CD4+ T cells in spleen. Moreover, Foxp3 mRNA levels of salivary glands were diminished in anti-B7-H4 mAb-treated mice. Flow cytometry analysis showed that anti-B7-H4 mAb inhibited CD4+Foxp3+/CD4+ T cell production, while B7-H4Ig would promote naïve CD4+ T into Treg differentiation. Administration with B7-H4Ig displayed significantly decreased lymphocyte infiltration in salivary glands and low levels of total IgM and IgG in serum. Analysis of inflammatory cytokines in salivary glands after B7-H4Ig treatment revealed that the mRNA levels of IL-12, IL-6, IL-18, IL-1α, TNF-α, and IFN-α were significantly downregulated in B7-H4Ig-treated mice compared to control Ig treatment. B7-H4Ig-treated mice had significantly higher levels of CD4+Foxp3+/CD4+ T cells in spleen. IHC in salivary gland revealed that CD4+Foxp3+ T cells of B7-H4Ig treatment mouse were more than control Ig treatment. Conclusions Our findings implicate that B7-H4 has a protective role for salivary gland epithelial cells (SGECs) and therapeutic potential in the treatment of pSS.

IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis

BackgroundCytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients.MethodsA total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses.ResultsA total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49–73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05–119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively.ConclusionsHigh-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.

SARS-CoV-2 serology and virology trends in donors and recipients of convalescent plasma

SARS-CoV-2 has infected millions worldwide. The virus is novel, and currently there is no approved treatment. Convalescent plasma may offer a treatment option. We evaluated trends of IgM/IgG antibodies/plasma viral load in donors and recipients of convalescent plasma. 114/139 (82 %) donors had positive IgG antibodies. 46/114 donors tested positive a second time by NP swab. Among those retested, the median IgG declined (p < 0.01) between tests. 25/139 donors with confirmed SARS-CoV-2 were negative for IgG antibodies. This suggests that having had the infection does not necessarily convey immunity, or there is a short duration of immunity associated with a decline in antibodies. Plasma viral load obtained on 35/39 plasma recipients showed 22 (62.9 %) had non-detectable levels on average 14.5 days from positive test versus 6.2 days in those with detectable levels (p < 0.01). There was a relationship between IgG and viral load. IgG was higher in those with non-detectable viral loads. There was no relationship between viral load and blood type (p = 0.87) or death (0.80). Recipients with detectable viral load had lower IgG levels; there was no relationship between viral load, blood type or death.

Reverse Angle: Immunological Evaluation of Patients with Bronchiectasis

Objective: Bronchiectasis is a chronic debilitating disease of the airways that results in chronic cough and production of viscous sputum due to dilatation of the airways and bronchial wall thickening. Although bronchiectasis is a common problem in immunodeficiencies and a well-known complication of these disorders, there are a limited number of studies on the frequency of immune abnormalities in adult patients with bronchiectasis. Materials and Methods: The records of adult patients who visited the Pulmonology Outpatient Clinic and whose immune system was assessed due to bronchiectasis at the Immunology Outpatient Clinic until June 2018 were retrospectively evaluated. The data of 84 patients with bronchiectasis (mean age: 48.5 ± 17.9 years, female: 45 [53.6%], male: 39 [46.4%]) were analyzed. Results: Six patients (7.1%) had at least one antibody deficiency. Four patients (4.8%) had low IgG levels, one (1.2%) had low IgA level, and one (1.2%) had low IgM level. Fourteen patients (16.7%) had high IgG (16-22 g/l), 10 (11.9%) high IgA (4.08 - 6.60 g/l) and one (1.2%) high IgM (8.87 g/l). Thirty-five patients (41.7%) had at least one abnormality in the peripheral lymphocyte subset analyses. Conclusion: Adult patients with bronchiectasis may have a variety of immunological abnormalities in addition to hypogammaglobulinemia. Therefore, clinicians should not overlook immunological evaluation in the etiological investigation of bronchiectasis, and patients with immunological abnormalities should be closely monitored.

Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19.

Introduction: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in COVID-19 patients.Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients at a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared between severe and non-severe patients. Immune response phenotyping based on the late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratified patients into different disease severities and outcomes.Results: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those with low IgG levels (51.8 vs. 32.3%; p = 0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p < 0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher inflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p < 0.05). Recovery rates for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype were 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p = 0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes.Conclusions: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on the late IgG response and NLR could act as a simple complementary tool to discriminate between severe and non-severe COVID-19 patients, and further predict their clinical outcome.

Novel CD40LG Mutation in Two Cousins With Immunoglobulin Class Switch Recombinant Deficiency

The hyper-immunoglobulin M (HIGM) syndrome comprises a group of rare inherited immunodeficiency disorders characterized by normal or elevated levels of serum IgM with low or absent levels of serum IgG, IgA, and IgE. Patients with this syndrome usually present with a history of recurrent infections or opportunistic infections. Here, we report two male cousins from homozygote twin mothers. The first cousin presented with no signs or symptoms other than neutropenia, which was accidentally found in a routine blood test. Immunological workup in this patient showed undetectable IgG and IgA levels and normal IgM levels. The second cousin had a history of recurrent infections, and at the time of admission, he was diagnosed with Pneumocystis jirovecii infection. The immunologic workup of this patient showed undetectable IgG, decreased IgA, and increased IgM level. Due to their interesting family relationship, genetic analysis was performed, which detected a novel mutation in exon 2 (c.266 del G) of the CD40 ligand gene (CD40LG).