The prognostic significance of early troponin levels in patients undergoing aortic ridge surgery.

Subaortic stenosis is a CHD that can lead to left ventricular hypertrophy, heart failure, and aortic valve damage if left untreated. The gold standard treatment for subaortic stenosis is septal myectomy. However, there is no clear consensus on the surgical margins required for adequate muscle resection. In this retrospective study, we reviewed the records of 83 patients who underwent subaortic stenosis surgery between 2012 and 2020 to investigate the effect of early troponin levels on prognosis. We excluded patients with additional cardiac pathologies, hypertrophic obstructive cardiomyopathy, and valvular aortic stenosis.Troponin levels were recorded in the early post-operative period, and patients were monitored for complications such as ventricular arrhythmia, left ventricular systolic dysfunction, infective endocarditis, and pacemaker implantation. The troponin levels were significantly higher in the patients who had septal myectomy. The degree of myectomy affected the risk of complications in the early post-operative period and recurrence in the later period. However, when the gradient was substantially or completely removed by myectomy, patients experienced significant symptom improvement in the early post-operative period, and their late survival was equivalent to that of healthy individuals of the same age.Our findings suggest that monitoring troponin levels in patients undergoing septal myectomy may be beneficial in predicting the risk of complications. However, further studies are needed to establish the optimal surgical technique and extent of muscle resection required for subaortic stenosis treatment. Our study adds to the existing knowledge of the benefits and risks associated with septal myectomy as a treatment option for subaortic stenosis.

An Investigation of temporomandibular pain, headache, and fatigue in relation with long-term mask use during the COVID-19 pandemic period.

OBJECTIVE: To investigate the effects of long-term mask use on temporomandibular pain, headache, and fatigue during the COVID-19 pandemic period via a survey. METHODS: The survey was sent online, and symptoms associated with mask use, perception of mask discomfort, temporomandibular dysfunction, fatigue, headache, and trigger points of temporomandibular joint were evaluated. RESULTS: For the study, 909 people were screened. Head, neck, face, throat, ear, and jaw pain, cheek tension, teeth clamping, acne, mask trace, palpitation, and voice and sleep disorders were different between groups (p < 0.05). The individuals' temporomandibular dysfunction and fatigue were different between groups (p < 0.05). CONCLUSION: Long-term mask use can cause many symptoms, such as headache, jaw pain, and fatigue. Furthermore, increased mask-wearing time can trigger all these symptoms. The authors recommend relaxing breaks and exercises for neck, jaw, and face muscles along with the use of appropriate masks to minimize negative symptoms.

A gray zone in the literature: indications, options, and outcomes for surgical repair of pulmonary artery aneurysms.

Pulmonary artery aneurysms are rare. They are characterised by an aneurysmatic dilatation of the pulmonary vascular bed, including the main pulmonary artery or the accompanying pulmonary artery branches. Increases in pulmonary flow and pulmonary artery pressure increase the risk of rupture: when these conditions are detected, surgical intervention is necessary.This study is a retrospective analysis of 33 patients treated in our paediatric cardiac surgery clinic from 2012 to 2020. Aneurysms and pseudoaneurysms in patients who were patched for right ventricular outflow tract reconstruction and corrected with a conduit were excluded from the study. Seventeen (51.5%) of the patients included in the study were female and 16 (48.5%) were male. The patients were aged between 23 and 61 years (mean 30.66 ± 12.72 years). Graft interpositions were performed in 10 patients (30.3%) and pulmonary artery plications were performed in 23 patients (69.7%) to repair aneurysms. There was no significant difference in mortality between the two groups (p > 0.05).Pulmonary artery aneurysm interventions are safe, life-saving treatments that prevent fatal complications such as ruptures, but at present there is no clear guidance regarding surgical timing or treatment strategies. Pulmonary artery interventions should be performed in symptomatic patients with dilations ≥5 cm or asymptomatic patients with dilations ≥8 cm; pulmonary artery pressure, right ventricular systolic pressure, and pulmonary artery aneurysm diameter must be considered when planning surgeries, their timing, and making decisions regarding indications. Experienced surgical teams can achieve satisfactory results using one of the following surgical techniques: reduction pulmonary arterioplasty, plication, or graft replacement.

Outcomes of home mechanical ventilation with tracheostomy after congenital heart surgery.

OBJECTIVE: After congenital heart surgery, some patients may need long-term mechanical ventilation because of chronic respiratory failure. In this study, we analysed outcomes of the patients who need tracheostomy and home mechanical ventilation. METHODS: Amongst 1343 patients who underwent congenital heart surgery between January, 2014 and June, 2018, 45 needed tracheostomy and HMV. The median age of these patients was 6.4 months (12 days-6.5 years). Nineteen patients underwent palliation while 26 patients underwent total repair. Post-operative diaphragm plication was performed in five patients (11%). Median duration of mechanical ventilation before tracheostomy was 32 days (8-154 days). The patients were followed up with their home ventilators in ward and at home. Mean follow-up time was 36.24 ± 11.61 months. RESULTS: The median duration of ICU stay after tracheostomy was 27 days (range 2-93 days). Follow-up time in ward was median 30 days (2-156 days). A total of 12 patients (26.6%) were separated from the ventilator and underwent decannulation during hospital stay. Thirty-two patients (71.1%) were discharged home with home ventilator support. Of them, 15 patients (46.9%) were separated from the respiratory support in median of 6 weeks (1 week-11 months) and decannulations were performed. Total mortality was 31.1%. in which four patients are still HMV dependent. There was no significant difference for decannulation between total repair and palliation patients. CONCLUSION: HMV via tracheostomy is a useful option for the treatment of children who are dependent on long-term ventilation after congenital heart surgery although there are potential risks.

Cascade screening and treatment of children with familial hypercholesterolemia in Turkey.

Objectives Premature coronary artery disease is the most common preventable cause of death in developed countries, and familial hypercholesterolemia (FH) is the most common monogenetic disorder of lipid metabolism, predisposing for premature coronary artery. FH is the most common preventable cause of death in developed countries. In 2016, the national lipid screening program in school-age children has been started in Turkey. In this study, we aimed to evaluate the efficacy of lipid screening program, lipid-lowering treatments, and the challenges of treatments in children diagnosed with FH. Methods Patients diagnosed with FH in the pediatric metabolism outpatient clinic were retrospectively evaluated. Changes in lipid profile with dietary interventions and statin treatments were assessed. The results of cascade screening were analyzed. Results Fifty-one patients diagnosed with FH were enrolled in the study. Twenty-four (47.1%) were female. The mean age of the patients was 9.8 ± 3.2 years. Heterozygous LDLR gene mutation was detected in all patients. Three novel pathogenic variations were revealed with the genetic investigation. Forty-one (80.4%) patients had high adherence to CHILD-2 dietary recommendations. The mean low-density lipoprotein cholesterol (LDL-C) level decreased by 14.5 ± 7.6% after dietary intervention. Parents refused to start statin treatment in 8 (15.7%) patients. Statin treatment was initiated to 22 (43.1%) patients. Mean LDL-C level decreased from 204.1 ± 19.1 mg/dL to 137.0 ± 13.1 mg/dL. In cascade screening, 7 (13.7%) parents without a diagnosis of FH were diagnosed with FH. After the screening program, statin treatment was initiated for 18 (35.3%) parents and 7 (16.3%) siblings. Conclusions We can conclude that screening for FH in children is crucial for diagnosing FH not only in children but also in their relatives. Although statins are safe and effective in achieving the target LDL-C level, we determined significant resistance for initiating statin treatment in patients.

Pentoxifylline and Pentaglobin adjuvant therapies for neonatal nosocomial sepsis in neonates less than 1500g weight.

OBJECTIVE: To compare different support therapies in very low birth-weight preterm neonates with nosocomial sepsis. METHODS: This clinical pilot study was conducted at the Bagcilar Research and Training Hospital, Istanbul, Turkey, from September 2015 to November 2016. Preterm infants appropriately sized for a gestational age of < 32 weeks and < 1,500g were included in the study. Pentaglobin was initiated on the day of diagnosis of nosocomial sepsis to very low birth-weight preterm neonates as a support therapy in addition to antibiotics: 5 ml/kg per day of pentaglobin was infused over a four-hour period on three consecutive days. Pentoxifylline (5 mg/kg every 6 hours) was administered to premature infants with sepsis on three successive days. RESULTS: Of the 41 neonates, 19(46.3%) were girls and 22(53.7%) were boys. Vital signs, haematologic tables, peripheral blood smear left shift ratio, and blood-gas parameters did not differ significantly between the groups (p>0.05), but the C-reactive protein (mg/dl) values significantly decreased after pentoxifylline treatment (p<0.05). Coagulase-negative staphylococci were the most frequently isolated bacteria in the two groups (n=4; 19% vs. n=4; 20%). There was no difference in isolated microorganisms. There was no significant difference in intraventricular haemorrhage, necrotising enterocolitis, periventricular leukomalacia or symptomatic patent ductus arteriosus in the neonates when comparing the two groups and no systemic reactions were observed during adjuvant therapy in the preterm neonates (p>0.05). The total duration of hospitalisation was 49.46±13.52 days for the pentaglobin group and 44.21±11.1 days for the pentoxifylline group neonates. CONCLUSIONS: Pentoxifylline treatment for nosocomial sepsis decreased C-reactive protein levels and heart rate more than pentaglobin therapy.

Phosphatase PP2A is requisite for the function of regulatory T cells.

Homeostasis of the immune system depends on the proper function of regulatory T cells (T(reg) cells). Compromised suppressive activity of T(reg) cells leads to autoimmune disease and graft rejection and promotes anti-tumor immunity. Here we report a previously unrecognized requirement for the serine-threonine phosphatase PP2A in the function of T(reg) cells. T(reg) cells exhibited high PP2A activity, and T(reg) cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometry revealed that PP2A associated with components of the mTOR metabolic-checkpoint kinase pathway and suppressed the activity of the mTORC1 complex. In the absence of PP2A, T(reg) cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is required for the function of T(reg) cells and the prevention of autoimmunity.

TRIF signaling is essential for TLR4-driven IgE class switching.

The TLR4 ligand LPS causes mouse B cells to undergo IgE and IgG1 isotype switching in the presence of IL-4. TLR4 activates two signaling pathways mediated by the adaptor molecules MyD88 and Toll/IL-IR domain-containing adapter-inducing IFN-ß (TRIF)-related adaptor molecule (TRAM), which recruits TRIF. Following stimulation with LPS plus IL-4, Tram(-/-) and Trif(-/-) B cells completely failed to express Cε germline transcripts (GLT) and secrete IgE. In contrast, Myd88(-/-) B cells had normal expression of Cε GLT but reduced IgE secretion in response to LPS plus IL-4. Following LPS plus IL-4 stimulation, Cγ1 GLT expression was modestly reduced in Tram(-/-) and Trif(-/-) B cells, whereas Aicda expression and IgG1 secretion were reduced in Tram(-/-), Trif(-/-), and Myd88(-/-) B cells. B cells from all strains secreted normal amounts of IgE and IgG1 in response to anti-CD40 plus IL-4. Following stimulation with LPS plus IL-4, Trif(-/-) B cells failed to sustain NF-κB p65 nuclear translocation beyond 3 h and had reduced binding of p65 to the Iε promoter. Addition of the NF-κB inhibitor, JSH-23, to wild-type B cells 15 h after LPS plus IL-4 stimulation selectively blocked Cε GLT expression and IgE secretion but had little effect on Cγ1 GLT expression and IgG secretion. These results indicate that sustained activation of NF-κB driven by TRIF is essential for LPS plus IL-4-driven activation of the Cε locus and class switching to IgE.

Health-related quality of life in Turkish patients with ankylosing spondylitis: impact of peripheral involvement on quality of life in terms of disease activity, functional status, severity of pain, and social and emotional functioning.

Ankylosing spondylitis (AS) affects sacroiliac joints at early stages and may involve the axial skeleton at later stages of disease. Peripheral involvement usually occurs in lower extremities. When it develops early in the disease course, it is a predictor of more aggressive disease. The aim of this study is to evaluate health-related quality of life (HRQoL) in AS and to assess the impact of peripheral involvement on HRQoL domains in terms of disease activity, functional status, pain, and social and emotional functioning. Seventy-four AS patients were included. Peripheral involvement was present in 51.35 % of the patients. In 65.79 % of these cases the hips, in 31.58 % the knees, in 18.42 % the shoulders and in 13.16 % the ankles were affected. Patients were evaluated by Ankylosing Spondylitis Quality of Life (ASQoL), Short Form-36 (SF-36), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Functional Index (BASFI). ASQoL was strongly correlated with ASDAS, BASDAI, BASFI, and Bath Ankylosing Spondylitis Metrology Index (BASMI), severity of total pain, night pain, fatigue, morning stiffness and ESR. ASDAS and BASDAI showed the strongest correlation with ASQoL. Severity of total pain, functional status and severity of night pain followed it, respectively. Patients with peripheral involvement scored significantly lower in all subgroups of SF36 and significantly higher in ASDAS, BASDAI, BASFI, BASMI and ASQoL scores and levels of pain, night pain, fatigue and morning stiffness. Peripheral involvement is associated with more active disease and functional disability and has a negative influence on HRQoL including physical, social and emotional functioning.

Validity and reliability of the Turkish version of the Health Assessment Questionnaire for the Spondyloarthropathies.

The Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) was built by adding five new questions related with cervical and lumbar spine functions to HAQ by Daltroy et al. (in J Rheumatol 17(7):946-945, 1990). The aim of this study was to adapt the added five items into Turkish and then to test its reliability and validity. New questions were adapted to Turkish according to 'translation-back translation' method. Seventy-nine patients with ankylosing spondylitis were asked with the Turkish version of HAQ-S (HAQ-S TV). To assess, construct validity patients were evaluated by HAQ, Bath AS Functional Index (BASFI), Bath AS Disease Activity Index (BASDAI), Bath AS Metrology Index (BASMI), Maastricht AS Enthesitis Score (MASES), Ankylosing Spondylitis Quality of Life (ASQoL), and laboratory variables (erythrocyte sedimentation rate, C-reactive protein). Construct validity was investigated with Spearmann's rank correlation coefficient. Reliability of HAQ-S TV was assessed by internal consistency. Inter- and intra-observer reliability were tested with Cronbach's alpha score. HAQ-S TV met set criteria of reliability and validity. Reliability of adapted version was found good with high internal consistency value. (Cronbach's alpha = 0.89). In addition to this intra-observer and inter-observer reliability were found adequate for total score of HAQ-S (Cronbach's alphas: 0.999 and 0.998 in order) and also for each added five questions (Cronbach's alphas >0.7). Positive correlations were found between HAQ-S TV and HAQ, BASFI, BASDAI, BASMI, MASES, ASQoL, ESR, and CRP (P < 0.05). The results of this study showed that HAQ-S TV was reliable and valid in patients with AS.

Toll-like receptor 9, transmembrane activator and calcium-modulating cyclophilin ligand interactor, and CD40 synergize in causing B-cell activation.

BACKGROUND: B cells receive activating signals from T cells through CD40, from microbial DNA through Toll-like receptor (TLR) 9, and from dendritic cells through transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI). TLR9 and CD40 ligation augment TACI-driven B-cell activation, but only the mechanism of synergy between CD40 and TACI has been explored. Synergy between CD40 and TLR9 in B-cell activation is controversial. OBJECTIVE: We sought to examine the mechanisms by which TLR9 modulates CD40- and TACI-mediated activation of B cells and to determine whether all 3 receptors synergize to activate B cells. METHODS: Naive murine B cells and human PBMCs were stimulated with combinations of anti-CD40, CpG, and a proliferation inducing ligand in the presence of IL-4. Proliferation was measured by means of tritiated thymidine incorporation. Immunoglobulin production was measured by means of ELISA. Class-switch recombination (CSR) was examined by measuring mRNA for germline transcripts, activation-induced cytidine deaminase (AICDA), and mature immunoglobulin transcripts. Plasma cell differentiation was examined by using syndecan-1/CD138 staining and mRNA expression of B lymphocyte-induced maturation protein 1 (Blimp-1). RESULTS: TLR9 synergized with CD40 and TACI in driving CSR and inducing IgG(1) and IgE secretion by naive murine B cells and synergized with TACI in driving B-cell proliferation and plasma cell differentiation. All 3 receptors synergized together in driving murine B-cell proliferation, CSR, plasma cell differentiation, and IgG(1) and IgE secretion. TLR9 synergized with CD40 and TACI in driving IgG secretion in IL-4-stimulated human B cells. CONCLUSION: Signals from TLR9, TACI, and CD40 are integrated to promote B-cell activation and differentiation.

Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking.

The F-BAR domain containing protein CIP4 (Cdc42 interacting protein 4) interacts with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of filamentous actin. CIP4(-/-) mice had normal T- and B-lymphocyte development but impaired T cell-dependent antibody production, IgG antibody affinity maturation, and germinal center (GC) formation, despite an intact CD40L-CD40 axis. CIP4(-/-) mice also had impaired contact hypersensitivity (CHS) to haptens, and their T cells failed to adoptively transfer CHS. Ovalbumin-activated CD4(+) effector T cells from CIP4(-/-)/OT-II mice migrated poorly to antigen-challenged skin. Activated CIP4(-/-) T cells exhibited impaired adhesion and polarization on immobilized VCAM-1 and ICAM-1 and defective arrest and transmigration across murine endothelial cell monolayers under shear flow conditions. These results demonstrate an important role for CIP4 in integrin-dependent T cell-dependent antibody responses and GC formation and in integrin-mediated recruitment of effector T cells to cutaneous sites of antigen-driven immune reactions.

The murine equivalent of the A181E TACI mutation associated with common variable immunodeficiency severely impairs B-cell function.

TNFRSF13B, which encodes TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor), is mutated in 10% of patients with common variable immune deficiency (CVID). One of the 2 most common TACI mutations in CVID, A181E, introduces a negative charge into the transmembrane domain. To define the consequence of the A181E mutation on TACI function, we studied the effect of its murine equivalent, mTACI A144E, on TACI signaling in transfected cells and on TACI function in transgenic mice. The mTACI A144E mutant, like its human TACI A181E counterpart, was expressed on the surface of 293T transfectants and was able to bind ligand, but exhibited impaired constitutive and ligand-induced NF kappaB signaling. In addition, constitutive and ligand-induced clustering of the intracellular domain was deficient for A144E as measured by fluorescence resonance energy transfer. Transgenic mice expressing the A144E mutant on TACI(-/-) background had low serum IgA levels and significantly impaired antibody responses to the type II T-independent antigen TNP-Ficoll. B cells from A144E transgenic mice were impaired in their capacity to proliferate and secrete IgG1 and IgA in response to TACI ligation. These results suggest that mTACI A144E mutation and its human counterpart, A181E, disrupt TACI signaling and impair TACI-dependent B-cell functions.

Transmembrane activator, calcium modulator, and cyclophilin ligand interactor drives plasma cell differentiation in LPS-activated B cells.

BACKGROUND: Transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) expression on B cells is upregulated by Toll-like receptor (TLR) 4. OBJECTIVE: We sought to examine whether TACI synergizes with TLR4 in driving immunoglobulin production by B cells and to examine the mechanism of this synergy. METHODS: Purified mouse naive B cells were stimulated with the TACI ligand a proliferation-inducing ligand (APRIL) and with suboptimal concentrations of the TLR4 ligand LPS in the presence or absence of IL-4. Immunoglobulin secretion was measured by means of ELISA. Surface IgG1-positive B cells and CD138+ plasmacytoid cells were enumerated by means of FACS. Expression of gamma1 and epsilon germline transcripts, activation-induced cytidine deaminase, and gamma1 and epsilon mature transcripts was measured by means of RT-PCR. RESULTS: APRIL synergized with LPS in driving B-cell proliferation and IgM, IgG1, IgG3, IgE, and IgA production. This was mediated by TACI because it was preserved in B-cell maturation antigen-/-, but not TACI-/-, B cells. APRIL and LPS synergized to promote isotype switching, as evidenced by increased expression of activation-induced cytidine deaminase and gamma1 and epsilon mature transcripts and generation of surface IgG1-positive cells. More importantly, APRIL and LPS strongly synergized to drive the plasma cell differentiation program, as evidenced by an increase in CD138+ cells and expression of B lymphocyte induced maturation protein-1 (Blimp-1), interferon regulatory factor-4 (IRF-4), and the spliced form of X-box binding protein-1 (XBP-1). TACI-/- mice had impaired IgM and IgG1 antibody responses to immunization, with a suboptimal dose of the type I T cell-independent antigen 2, 4, 6- Trinitrophenol (TNP)-LPS. CONCLUSIONS: These observations suggest that TACI cooperates with TLR4 to drive B-cell differentiation and immunoglobulin production in vitro and in vivo.

Primary immune deficiencies with aberrant IgE production.

IgE antibodies play a central role in the pathogenesis of atopic diseases and in host immunity against parasitic infections. IgE has potent activities on mast cells and basophils. IgE class switching is a very tightly controlled process, and serum IgE levels are very low compared with other immunoglobulin isotypes. Transcription factors that activate or inhibit the IgE gene promoter, as well as T(H)1 and T(H)2 cytokines are important in the regulation of IgE levels. Hyper-IgE syndrome; Wiskott-Aldrich syndrome; immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX); Omenn syndrome; and atypical complete DiGeorge syndrome are primary immune deficiencies that are associated with elevated serum IgE levels. Increased IgE levels in IPEX, Wiskott-Aldrich syndrome and Omenn syndrome are likely related to increased T(H)2 cytokine production caused by decreased a number or function of CD4(+)CD25(+)forkhead box protein P3(+) regulatory T cells. The link between signal transducer and activator of transcription 3 mutations and elevated serum IgE levels in hyper-IgE syndrome is unclear. Insight into IgE regulation provided by the study of primary immune deficiencies with elevated IgE has important implications for allergic diseases.

Transmembrane activator and calcium-modulator and cyclophilin ligand interactor mutations in common variable immunodeficiency.

PURPOSE OF REVIEW: TNFRSF13B, the gene which encodes transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is mutated in nearly 10% of patients with common variable immune deficiency (CVID), an antibody deficiency syndrome characterized by loss of memory B cells and plasma cells. This review discusses the normal function of TACI and the role of TACI mutants in CVID. RECENT FINDINGS: TACI activates isotype switching, mediates immunoglobulin production in response to type II T-independent antigens, and plays an inhibitory role in B cell homeostasis. Recent evidence indicates that TACI synergizes with CD40 and Toll-like receptors for immunoglobulin secretion and promotion of plasma cell differentiation. The two most common TACI mutants associated with CVID--C104R and A181E--are primarily found as heterozygous mutations suggesting that they either cause haploinsufficiency or exert a dominant negative effect. TACI mutations in CVID are associated with an increased susceptibility to autoimmunity and lymphoproliferation. SUMMARY: TACI has a dual function in promoting B cell antibody responses and inhibiting B cell proliferation. The observation that TACI mutations are present in healthy participants suggests that modifier genes may play an important role in the development of CVID. The discovery of these genes will help understand the pathogenesis of this disease.

Transmembrane activator and calcium modulator and cyclophilin ligand interactor enhances CD40-driven plasma cell differentiation.

BACKGROUND: Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor used by B cell-activating factor of the TNF family and a proliferation-inducing ligand (APRIL) to induce isotype switching independently of CD40 and is mutated in patients with common variable immunodeficiency. OBJECTIVE: We sought to determine whether TACI and CD40 cooperate in inducing class switch recombination and immunoglobulin production. METHODS: Naive mouse B cells were stimulated with suboptimal concentrations of anti-CD40 plus IL-4 in the presence or absence of APRIL or anti-TACI. IgG(1) and IgE production was measured by means of ELISA. mRNA for Cgamma(1) and Cepsilon germ-line transcripts, activation-induced cytidine deaminase, and mature gamma(1) and epsilon transcripts were measured by means of RT-PCR. Plasmablasts were enumerated by using syndecan-1/CD138 staining. Interferon regulatory factor 4, B lymphocyte-induced maturation protein 1, and IL6 mRNA expression was measured by using quantitative PCR. RESULTS: TACI ligation enhanced IgG(1) and IgE secretion by naive murine B cells stimulated by anti-CD40 plus IL-4, with little effect on B-cell proliferation or class switch recombination. In contrast, TACI ligation of anti-CD40 plus IL-4-stimulated B cells induced a significant increase in syndecans-1/CD138-positive cells. TACI ligation caused a modest but significant increase in the expression of interferon regulatory factor 4, with no detectable change in B lymphocyte-induced maturation protein 1 expression. CONCLUSION: TACI and CD40 signaling converge to promote B-cell differentiation into plasmablasts. CLINICAL IMPLICATIONS: Our data suggest that TACI dysfunction could contribute to the impaired antibody response to T-dependent antigens in common variable immunodeficiency.