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Respiratory infections caused by Chlamydia pneumoniae have been associated with exacerbations of asthma. Cell-mediated immunity ( CMI) is critical for maintaining immunity. We compared interferon ( IFN)- γ responses in C. pneumoniae-infected peripheral blood mononuclear cells ( PBMC) in paediatric patients ± asthma. Presence of C. pneumoniae was tested from asthma patients (N = 17) and non-asthmatic controls ( N = 16) ( PCR). PBMC were infected for 1 h ± C. pneumoniae AR-39 ( MOI = 0.1) and cultured for 48 h. IFN- γ levels were measured in supernatants ( ELISA). C. pneumoniae-IgG antibodies in serum were determined ( MIF). All subjects tested negative for C. pneumoniae ( PCR). C. pneumoniae-induced IFN- γ production in vitro was more prevalent in asthma compared with non-asthma; levels of IFN- γ were higher in asthma compared with non-asthma ( P = 0.003). There was no association between recent respiratory infection and positive IFN- γ responses. These data show that C. pneumoniae modulates IFN- γ responses in patients with asthma, even in absence of active infection. [ABSTRACT FROM AUTHOR]

Immunoglobulin (Ig) E may provide immunity against Borrelia burgdorferi infection (Lyme disease) in children which lasts throughout adulthood. We investigated the presence and persistence of IgE anti- B. burgdorferi antibodies (Abs) in paediatric patients infected with Lyme disease over time. Serum immunoglobulin levels, presence of IgG and IgE anti- B. burgdorferi components, and distributions of blood T, B and natural killer lymphocyte subsets were studied in B. burgdorferi-infected and -uninfected children (nephelometry, UniCAP Total IgE Fluoroenzymeimmunoassay, Western blot, flow cytometry). Total serum IgM, IgG, IgE and IgA levels, and distributions of blood lymphocytes (CD4+, CD8+, CD19+) of both groups, excluding CD8+CD60+ T cells, were within normal ranges. However, infected, but not uninfected children made IgG anti- B. burgdorferi proteins p18, p31, p34, p41, p45, but not IgG anti-p60, and IgE anti- B. burgdorferi proteins p31, p34, p41, p45, p60, but not IgE anti-p18. These proteins were also detected in an infected child 1 year post-infection. Interestingly, CD8+CD60+ T-cell numbers were significantly increased (fourfold) in infected, compared with uninfected, patients ( P = 0.001). These results demonstrate that specific IgE anti- B. burgdorferi Abs are generated and persist in children with Lyme disease and that CD8+CD60+ T cells may play an important role in these responses. [ABSTRACT FROM AUTHOR]

Objective: To present the case of a solid organ transplant recipient with a rash, which might be a drug allergy mimic., Case Report: We present a 62-year-old male lung transplant recipient, who experienced a sudden erythematous rash two months post-transplant after he was given new medications for his transplant status. Physical examination by the team revealed the patient had a generalized flat, polymorphic papular rash with pinpoint crusting and associated excoriations. Skin biopsy indicated purpuric interface dermatitis with eosinophils, which suggested a drug reaction. In the workup process, patient was admitted for Rhinovirus (HRV) infection and placed on 30 mg prednisone tapering. His rash slowly resolved with discontinuation of Bactrim and Voriconazole. His overall clinical picture was concerning for a drug allergy, but he was on high-dose systemic corticosteroid regimen (Prednisone 40 mg daily) which hindered drug allergy testing., Conclusion: Findings suggest a potential drug allergy or drug reaction, but workup was limited. Thus, the consulting clinician could consider this case a drug allergy mimic or should consider other medical conditions. Challenges exist in identifying a correct differential diagnosis of drug allergy in clinically complicated transplant patients; misdiagnosis may occur, which might lead to delayed care. There is a need for alternative differential diagnostic strategies and treatment options., (© 2024 by the Association of Clinical Scientists, Inc.)

Objective: Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has been known to cause immune dysregulation. However, the association between specific immunoglobulins and clinical characteristics in COVID-19 remains poorly understood. This study investigated the relationship between immunoglobulins and clinical outcomes in adults hospitalized with COVID-19 pneumonia., Methods: A retrospective chart analysis was performed (N=569, December 2020-April 2021). Information on demographics, clinical factors, and total serum immunoglobulin (IgG, IgA, IgM, and IgE) levels were collected (N=60). Clinical outcomes of interest included: symptom duration, comorbidities (Charlson 10-year-estimated-survival (C10YES) and comorbidity index (CCI), vital derangements upon presentation (NEWS-2-score), length of stay (LOS), and mortality. Spearman correlation, chi-square tests and linear regression were conducted., Results: Serum IgM levels were positive predictors of C10YES (β=0.104, p =0.023) and negative predictors of CCI (β=-0.007, p =0.047). There was an association between higher serum IgG levels and longer LoS (β=7.455, p =0.047). We found no significant associations between immunoglobulins and preadmission symptom duration, medication use, or mortality., Conclusions: Total IgM was associated with increased survival and decreased comorbidity, and total IgG was associated with length of hospitalization. IgM may predict the body's initial ability to produce humoral immune responses, and IgG may function as a possible signature of chronic antigenic responses and inflammation, associated with comorbidities that increase COVID-19 hospitalization. Evaluating total IgM and IgG as prognostic biomarkers in COVID-19 pneumonia patients may contribute to improved management and clinical outcomes., (© 2023 by the Association of Clinical Scientists, Inc.)

Context: The regeneration protein family (Reg), which includes Reg I and PAPII, is expressed in pancreas acinar cells, and increases in acute pancreatitis. We have demonstrated that Reg gene knockdown worsens severity of acute pancreatitis in the rat and hypothesize that the proteins offer a protective effect in this disease., Objective: We investigated the ability of anti-Reg and anti-PAP antibody to neutralize pancreatic Reg protein and affect pancreatitis severity., Intervention: Pancreatitis was induced in rats by retrograde ductal injection of 4% sodium taurocholate., Animals: Eighty-four rats: 48 with induced pancreatitis, 30 sham operated, and 6 normal animals., Setting: Intraductal anti-Reg I and/or anti-PAPII antibody was administered at induced pancreatitis and sham operated subgroups of 6 rats each., Main Outcome Measure: Serum and pancreata were harvested 24 and/or 48 hours later and assessed for pancreatitis severity by pancreatic wet weight, serum C-reactive protein (CRP), amylase, PAPII levels, and histopathology., Results: Animals induced with pancreatitis with administration of anti-Reg/PAP antibodies had significantly higher wet weights compared with taurocholate and histopathological analysis revealed that anti-Reg/PAP treated animals had worse tissue inflammation and necrosis compared with controls. Serum CRP, amylase, and Reg levels did not significantly differ between experimental and sham control groups., Conclusions: Administration of anti-Reg/PAP antibody worsened taurocholate-induced organ specific pancreatitis. These data suggest that the Reg family of proteins is protective in acute pancreatitis.

Objectives: Pancreatitis-associated proteins (PAPs) are induced in acute pancreatitis and antisense-mediated gene knockdown of PAP decreased PAP gene expression and worsened pancreatitis. Here, we investigated the effect of a more stable inhibition of PAP using small-interference RNA gene knockdown in vitro and in an in vivo model of experimental pancreatitis., Methods: Pancreatitis-associated protein-specific siRNA was administered to AR42J cell cultures or rats induced with pancreatitis. Controls included administration of scrambled siRNA or vehicle alone. After 24 hours, cells and pancreata were harvested and assessed for PAP (PAP 1, PAP 2, PAP 3) gene expression and pancreatitis severity., Results: In vitro, PAP protein, and mRNA levels were reduced (PAP 1, 76%; PAP 2, 8%; PAP 3, 24%) in cells treated with PAP siRNA. In vivo, PAP 1, and PAP 3 expressions were reduced (PAP 1, 36%; PAP 3, 66%) in siRNA-treated rats; there was no difference in PAP 2 isoform mRNA expression and serum protein levels. Serum amylase and lipase levels decreased (> or =50%) after administration of siRNA; interleukin (IL) 1beta, IL-4, and IL-6 increased, whereas C-reactive protein and tumor necrosis factor-alpha decreased when compared with vehicle control. Administration of PAP siRNA correlated with worsening histopathology., Conclusions: siRNA-mediated gene knockdown of PAP worsens pancreatitis. Differences in gene knockdown technology may provide different approaches to study gene function.

Although many immunoglobulin-related drug sensitivities have been described, there is a paucity of reports regarding IgE-related drug sensitivities. Here we describe a case of a patient who demonstrated IgE-mediated sensitivity to ibuprofen.

We previously identified a group of long-term pediatric survivors who had acquired HIV-1 through maternal transmission; had not received antiretroviral therapy; are now >8 years old, in good health, and with no opportunistic infections; and have not failed to thrive, although they have greatly decreased numbers of blood CD4+ T cells (<500/mm(3)). All the children have elevated total serum IgE levels (210-2475 IU/ml) and make anti-HIV-1 IgE or IgE directed against non-HIV-1 specificities (radioimmunoassay, Western blot assay); they have no detectable antigenemia. We have now studied the ability of anti-HIV-1 IgE in serum obtained from these children to regulate (1) production of HIV-1 by interleukin 2/phytohemagglutinin (IL-2/PHA)-stimulated peripheral blood mononuclear cells (PBMCs) taken from HIV-1-seronegative donors and infected with a T cell-tropic clone of HIV-1, and (2) transmission of a primary HIV-1 strain from adult AIDS patients to uninfected IL-2/PHA-stimulated PBMCs (p24 core antigen production). High levels of HIV-1 production were observed when PBMCs were cultured for 5 days in the presence of HIV-1-seronegative donor serum that was either IgE positive or IgE negative (IgE, >100 or <100 IU/ml, respectively). HIV-1 production also was observed when PBMCs were cultured with HIV-1-infected donor serum that either contained IgE directed against non-HIV-1 specificities or was IgE negative; these levels were 40% less than those seen with sera from the HIV-1-seronegative donors. Far greater inhibition of virus production was observed if the serum in culture contained anti-HIV-1 IgE (>95%). Virus neutralization did not appear to account for the inhibition obtained with anti-HIV-1 IgE-containing serum because virus production was not suppressed in cultures to which serum was added immediately preinfection (<10%), but was strongly suppressed when serum was added 1.5 hr postinfection (>95%). The inhibition of virus production obtained with serum containing anti-HIV-1 IgE was reversed when (1) serum was depleted of IgE (immunoaffinity), but not when it was depleted of IgG (protein G-Sepharose) before inclusion in culture postinfection, (2) anti-IgE, but not anti-IgG, was included in culture, or (3) serum was heat treated before culture. The results indicate that serum from certain HIV-1-infected pediatric long-term survivors contains agents that inhibit HIV-1 production in vitro, and that these agents include anti-HIV-1 IgE. They suggest that a cytotoxic event, rather than virus neutralization, plays an important role in anti-HIV-1 IgE-mediated inhibition of virus production.

To determine the contribution of B cells to brain myelin injury in Semliki Forest Virus (SFV) encephalomyelitis, normal C57BL/6 (B6) and B-cell-deficient (C57BL/6-tm1Cgn) B6 mice were infected with SFV. The peak of clinical disease, i.e., the time at which the greatest proportions of mice had moderate to severe clinical signs, appeared earlier in B6 mice [day 7 postinfection (pi)] than in B-cell-deficient mice (day 21 pi). By flow cytometry, no clear differences were found in the percentages of CD3(+)CD4(+) T cells in the brains of B6 and B-cell-deficient mice. However, by day 21 pi, percentages of CD3(+)CD8(+) T cells were greater in brains of B-cell-deficient than in those of B6 mice. On day 21 pi, percentages of CD19(+) B cells were maximal in B6 mice, but B cells were absent in B-cell-deficient mice at all time points. Sera obtained from B6 mice showed antibody responses to SFV, to SFV E2 peptides p137-151 and p115-133, and to peptides of myelin oligodendrocyte glycoprotein p18-32 and myelin basic protein (MBP) p64-75. Sera obtained from B-cell-deficient mice showed minimal or no reactivity to SFV, E2, or myelin peptides. CNS inflammatory and PAS-positive macrophage foci were maximal on days 7-14 pi in all mice. Additionally, B6 mice had brain white matter vacuolation, whereas B-cell-deficient mice did not. These data suggest that brain infiltrating B cells and anti-myelin antibodies contribute to myelin injury in SFV encephalomyelitis., (Copyright 2000 Academic Press.)

To determine the role of immune responses in the etiology of coronary angioplasty, the distribution of blood lymphocytes and levels of soluble immune factors in sera of patients with primary unstable angina were determined at pre and post coronary angioplasty. Our data showed (1) an increase in the numbers of lymphocytes bearing lymphocyte activating gene-3 (LAG-3) and CD40 in the blood and (2) an increase in levels of sIL2-R and sVCAM-1 in the sera of patients with unstable angina, compared with normal subjects. In contrast, there were no changes in these values in blood or sera of patients shortly after coronary angioplasty. However, levels of sCD8 in the sera of patients, which were similar to those of normal subjects, significantly increased post coronary angioplasty. These results indicate that peripheral blood lymphocytes of patients with unstable angina are immunologically activated and are producing soluble factors which may allow their interaction with endothelial cells in areas of inflammation. This may play a role in antigen presentation and T-B cell interactions which can lead to potentiation of heart disease., (Copyright 1999 Academic Press.)

To characterize the cellular basis of IgE responses in HIV-positive (HIV+) children, we obtained central (bone marrow [BM], thymus) and peripheral (Peyer's patches [PP], mesenteric [MLN], and other lymph nodes [OLN], spleen), lymphoid organs from two children with AIDS (females, 2 and 8 years old), and from a non-HIV-infected trauma victim (female, 5 years old) at autopsy. PP were obtained from one of the HIV+ children (2 yr old) and from the non-infected child, but no PP were detected in small intestine of the 8-yr-old HIV+ child. Numbers of lymphocytes bearing surface IgE, CD19, CD3, CD4, and CD8 in lymphoid organs were determined (flow cytometry) and evaluated for expression of epsilon-specific (E) mRNA (RT-PCR). Thymus and MLN of the HIV+ child without PP contained high numbers of IgE+ (34% and 41%, respectively) and CD19+ (32% and 28%, respectively) cells; IgE+ cells were not found in any other organ. In contrast, in the HIV+ child with PP, IgE+ cells were detected in all organs, except BM. The thymus of this child contained fewer CD19+ cells (7%). However, in both HIV+ children, all lymphoid organs, including thymus, contained E mRNA. Because numbers of IgE+ cells often far exceeded numbers of CD19+ B cells, and because CD8+ T cells predominated in all organs, some of the IgE+ cells were probably CD8+ T cells with cytophilic IgE and may include IgE-specific regulatory and/or memory T cells. IgE responses were not detected in the healthy trauma victim nor were B cells found in thymus. The data suggest that during HIV infection, IgE+ B cells may be found in thymus and that synthesis of IgE may occur in all lymphoid organs except BM.