Various clinical manifestations of 223 patients with IgE deficiency in a tertiary hospital in China: A cross-sectional study.

High Immunoglobulin E(IgE) levels associated with hypersensitivity or parasitic infection were well established, but the clinical significance of ultra-low IgE was largely unknown. Previous studies indicated these patients have an elevated risk of cancer, but large-scale epidemiological studies on the prevalence and clinical manifestations of these ultra-low IgE patients are still lacking. A total of 62,997 patients who were admitted to the First Affiliated Hospital of Wenzhou Medical University and had IgE level tests from January 2010 to March 2020 were included. Patients with serum IgE levels < 2 IU/mL were defined to have ultra-low IgE. And the clinical characteristics of these patients were retrospectively analyzed based on electronic medical record system and follow-up. A total of 223 patients (223/62,997, 0.35%) had ultra-low IgE were documented in 62,997 patients who had IgE tests. Among the clinical manifestations of these 223 ultra-low IgE patients, infection ranked first (125/223, 56.05%), following allergic diseases (51/223, 22.87%), hematological disorders (37/223, 16.59%), tumor (27/223, 12.11%) and autoimmune diseases (23/223, 10.31%). To the best of our knowledge, we first reported that the prevalence and clinical characteristics of 223 ultra-low IgE patients in China. The most common comorbidities were infection, allergic diseases, hematological disorders, tumor and autoimmune diseases.

The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient.

BACKGROUND: HIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. METHODS: From March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/µL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/µL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. RESULTS: Patients in low-CD4 group have lower proportion of CD3-CD56dimCD16+ NK cell subset, but have higher proportion of CD3-CD56-CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3-CD56-CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3-CD56-CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). CONCLUSIONS: There are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3-CD56-CD16+ NK cell subset before treatment is related with HAART efficacy.

The epidemiology and clinical feature of selective immunoglobulin a deficiency of Zhejiang Province in China.

BACKGROUND: Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency disease and frequently reported in the Western countries. However, large-scale epidemiologic studies on SIgAD in China are still lacking. METHODS: The clinical information of 555 180 subjects (age >4 years) including the outpatient, inpatient, and healthy subjects who had ordered serum immunoglobulin A, G, M in 9 hospitals of Zhejiang Province in China was collected. The SIgAD individuals were defined as IgA level <0.07 g/L with normal levels of serum IgG and IgM, whose age should be over 4 years, and any other secondary diseases causing SIgAD were also excluded. Then, the geographical and prevalence distribution of SIgAD individuals in Zhejiang Province and patients' clinical characteristics at the time of diagnosis were also reviewed. RESULT: Among these 555 180 subjects who had ordered the immunoglobulin evaluation, the prevalence of SIgAD was 109/555180 (0.02%). The ratio of male to female of these SIgAD individuals was 1:1.37, which also included 87 adults (≥18 years) and 22 children (18 > age >4 years). For adults, the common clinical features were infections (43/87, 49.43%), autoimmune disorders (31/87, 35.63%), allergic cases (5/87, 5.75%), and tumor cases (4/87, 4.60%). Additionally, infectious diseases (20/22, 90.91%), autoimmune disorders (4/22, 18.18%), and allergic cases (1/22, 4.55%) were found in 22 children. CONCLUSION: We first describe a large cohort of SIgAD individuals of Zhejiang Province in China. The incidence was 0.020%. The common clinical features were infection, autoimmune disorders, tumor, and allergy, and the infection rate was higher in children than the adults.

Contribution of a mitochondrial tyrosyl-tRNA synthetase mutation to the phenotypic expression of the deafness-associated tRNASer(UCN) 7511A>G mutation.

Nuclear modifier genes have been proposed to modify the phenotypic expression of mitochondrial DNA mutations. Using a targeted exome-sequencing approach, here we found that the p.191Gly>Val mutation in mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) interacts with the tRNASer(UCN) 7511A>G mutation in causing deafness. Strikingly, members of a Chinese family bearing both the YARS2 p.191Gly>Val and m.7511A>G mutations displayed much higher penetrance of deafness than those pedigrees carrying only the m.7511A>G mutation. The m.7511A>G mutation changed the A4:U69 base-pairing to G4:U69 pairing at the aminoacyl acceptor stem of tRNASer(UCN) and perturbed tRNASer(UCN) structure and function, including an increased melting temperature, altered conformation, instability, and aberrant aminoacylation of mutant tRNA. Using lymphoblastoid cell lines derived from symptomatic and asymptomatic members of these Chinese families and control subjects, we show that cell lines harboring only the m.7511A>G or p.191Gly>Val mutation revealed relatively mild defects in tRNASer(UCN) or tRNATyr metabolism, respectively. However, cell lines harboring both m.7511A>G and p.191Gly>Val mutations displayed more severe defective aminoacylations and lower tRNASer(UCN) and tRNATyr levels, aberrant aminoacylation, and lower levels of other tRNAs, including tRNAThr, tRNALys, tRNALeu(UUR), and tRNASer(AGY), than those in the cell lines carrying only the m.7511A>G or p.191Gly>Val mutation. Furthermore, mutant cell lines harboring both m.7511A>G and p.191Gly>Val mutations exhibited greater decreases in the levels of mitochondrial translation, respiration, and mitochondrial ATP and membrane potentials, along with increased production of reactive oxygen species. Our findings provide molecular-level insights into the pathophysiology of maternally transmitted deafness arising from the synergy between tRNASer(UCN) and mitochondrial YARS mutations.

Hypertension-associated mitochondrial DNA 4401A>G mutation caused the aberrant processing of tRNAMet, all 8 tRNAs and ND6 mRNA in the light-strand transcript.

Mitochondrial tRNA processing defects were associated with human diseases but their pathophysiology remains elusively. The hypertension-associated m.4401A>G mutation resided at a spacer between mitochondrial tRNAMet and tRNAGln genes. An in vitro processing experiment revealed that the m.4401A>G mutation caused 59% and 69% decreases in the 5' end processing efficiency of tRNAGln and tRNAMet precursors, catalyzed by RNase P, respectively. Using human umbilical vein endothelial cells-derived cybrids, we demonstrated that the m.4401A>G mutation caused the decreases of all 8 tRNAs and ND6 and increases of longer and uncleaved precursors from the Light-strand transcript. Conversely, the m.4401A>G mutation yielded the reduced levels of tRNAMet level but did not change the levels of other 13 tRNAs, 12 mRNAs including ND1, 12S rRNA and 16S rRNA from the Heavy-strand transcript. These implicated the asymmetrical processing mechanisms of H-strand and L-strand polycistronic transcripts. The tRNA processing defects play the determined roles in the impairing mitochondrial translation, respiratory deficiency, diminishing membrane potential, increasing production of reactive oxygen species and altering autophagy. Furthermore, the m.4401A>G mutation altered the angiogenesis, evidenced by aberrant wound regeneration and weaken tube formation in mutant cybrids. Our findings provide new insights into the pathophysiology of hypertension arising from mitochondrial tRNA processing defects.

D-Dimer levels are correlated with disease activity in Crohn's patients.

Various indices have been used to assess Crohn's disease (CD). However, the question of whether the Crohn's Disease Activity Index (CDAI) is associated with coagulation function has not been fully confirmed. In this study, we examined the association between CDAI and the coagulation and fibrinolysis parameters. In a retrospective and observational cohort study, the CDAI of 108 patients from two hospital centers was calculated, and its correlations with the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalization ratio (INR), fibrinogen (Fg) and plasma D-Dimer were investigated. Significant differences were found for PT, APTT, TT, INR, Fg and D-Dimer between the healthy controls and CD patients. However, no significant difference was found between the CDAI-High and CDAI-Low groups of CD patients. Moreover, the CDAI was positively correlated with the level of D-Dimer in CD patients of two hospitals, regardless of the detection method (hospital 1: r=0.3268, p= 0.0042; hospital 2: r=0.5553, p=0.0008). Among the blood coagulation and fibrinolysis parameters, the D-Dimer level was highly correlated with CDAI in CD patients. Thus, the level of D-Dimer expression may be a promising new marker for assessing CD disease activity.