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Objective:To determine the expression of transglutaminase 2 (TGM2) in peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD), and to analyze its correlation with AD-related inflammatory factors and disease severity.Methods:A total of 29 AD patients and 15 healthy controls were collected from the First Affiliated Hospital of Fujian Medical University from July 2020 to January 2021. Ten milliliters of peripheral blood samples were collected from each subject, so was the clinical information, including age, gender, course of disease, eosinophil counts, basophil counts, total IgE levels, Scoring AD index (SCORAD), etc. PBMCs were isolated by density gradient centrifugation. Fluorescence-based quantitative PCR was performed to determine the mRNA expression of TGM2 and AD-related inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17, thymic stromal lymphopoietin [TSLP], P2RX7 [purinergic receptor P2X, ligand-gated ion channel, 7], etc.) in PBMCs from 29 AD patients and 15 healthy controls, and flow cytometry to determine TGM2 protein expression on PBMCs. Mann-Whitney U test was used to analyze differences between groups, and Spearman correlation analysis to evaluate the correlation. Results:The relative mRNA expression of TGM2 in PBMCs did not differ between the AD group and control group ( M[ Q1, Q3]: 0.509 [0.325, 0.958] vs. 0.475 [0.328, 1.051], U = 210.50, P = 0.872). Compared with the control group, the AD group showed significantly decreased IL-4 mRNA expression (0.171[0.049, 0.449] vs. 0.824 [0.397, 1.378], P < 0.001), but significantly increased mRNA expression of IL-8 and IL-13 ( P = 0.011, 0.006, respectively). Spearman correlation analysis showed that the mRNA expression level of TGM2 in PBMCs was positively correlated with the mRNA expression levels of IL-4 and P2RX7 in the AD group ( rs = 0.42, 0.40, P = 0.024, 0.034, respectively), while there were no correlations between TGM2 mRNA expression and AD severity-related indicators (all P>0.05), such as age (21[16, 29] years), course of disease (4[1,10] years), eosinophil counts (0.33[0.18, 0.65] × 10 9/L), basophil counts (0.04[0.03, 0.06] × 10 9/L], SCORAD scores (60.5[46.98, 66.13] points), and serum total IgE levels (373 [40, 1 815] IU/ml). The relative protein expression levels of TGM2 on the surface of PBMCs did not differ between the AD group and control group (54.9 [47.6, 62.8] vs. 55.55 [51.5, 60.25], U = 112.00, P = 0.922) ], and no correlations were observed between the protein expression of TGM2 on PBMCs and AD severity-related indicators in the AD group (all P > 0.05) . Conclusion:No significant differences were observed in TGM2 mRNA expression in PBMCs or TGM2 protein expression on the surface of PBMCs between the AD patients and healthy controls, and there were no correlations between the TGM2 mRNA and protein expression and AD severity.
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Atopic dermatitis (AD) is closely related to many systemic diseases, such as other allergic diseases, autoimmune diseases, infectious diseases, cardiovascular diseases and mental disorders, and the underlying mechanism is very complex. AD is considered to be a starting point of the allergy march, and affects the occurrence of various allergic diseases such as food allergies, allergic rhinitis and allergic asthma. AD is associated with the occurrence of many autoimmune diseases, decreased incidence of some malignant tumors and low serum levels of vitamin D. AD is not only a potential risk factor for multiple organ infections and osteoporosis, but also increases the risk of cardiovascular diseases, nephrotic syndrome, and skin dryness. In addition, mental disorders such as anxiety and depression are also common complications of AD. To recognize and investigate into the associations between AD and systemic diseases is of great significance for improving the prognosis and quality of life of AD patients.
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A 59-year-old male patient presented with recurrent erythema and wheals all over the body for 6 years,complicated by irregular fever (the highest body temperature ＜ 39 ℃)and arthralgia for 2 months.He experienced a weight loss of 5 kg during two years prior to the presentation.Physical examination showed anemic comlexion,and there was no palpable enlargement of superficial lymph nodes,liver and spleen.Generalized erythema and wheals occurred all over the body,involving about 50％ of the body surface area.Histopathological examination of skin lesions showed infiltration of multiple neutrophilic granulocytes around blood vessels in the superficial dermis,and no vasculopathy was observed.Laboratory examinations revealed increased white blood cell (WBC) counts(13.97 × 109/L),erythrocyte sedimentation rate (ESR,136 mm/1 h) and C-reactive protein (CRP) level (75 mg/L),decreased hemoglobin level (96 g/L),and high serum levels of IgE (1 596 kU/L),IgG(20.4 g/L)and IgM(6 310 mg/L).Serum immunoelectrophoresis demonstrated that the IgM was a κ-type monoclonal immunoglobulin.Bone marrow examination showed active bone marrow hyperplasia.DNA sequencing analysis of 10 pairs of exons of the NLRP3 gene revealed 3 synonymous mutations,including c.663:C ＞ T:p.T221,c.732:G ＞ A:p.A244A and c.786:A ＞ G:p.R262R.Finally,the patient was diagnosed with Schnitzler's syndrome.There was no improvement of symptoms after the treatment with multiple oral antihistamines at increased dose levels.Then,the treatment protocol was adjusted to oral ciclosporin at a dosage of 200 mg/d for consecutive 18 days,but the patient still showed no response.After the treatment with oral prednisone (30 mg/d) and Tripterygium wilfordii tablets (66 μg thrice a day) for 2 weeks,the skin rashes subsided gradually,and arthralgia was relieved.Moreover,the WBC count,ESR and CRP level were decreased to 9.01 × 109/L,50 mm/1 h and 6 mg/L respectively,while the hemoglobin level was increased to 109.7 g/L.After 1-year follow-up,the dosage of glucocorticoids was gradually decreased to 8 mg/d.In addition,his condition was controlled well with no skin lesions and fever,except for occasional arthralgia in the knees and hip.
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A 59-year-old male patient presented with recurrent erythema and wheals all over the body for 6 years,complicated by irregular fever (the highest body temperature ＜ 39 ℃)and arthralgia for 2 months.He experienced a weight loss of 5 kg during two years prior to the presentation.Physical examination showed anemic comlexion,and there was no palpable enlargement of superficial lymph nodes,liver and spleen.Generalized erythema and wheals occurred all over the body,involving about 50％ of the body surface area.Histopathological examination of skin lesions showed infiltration of multiple neutrophilic granulocytes around blood vessels in the superficial dermis,and no vasculopathy was observed.Laboratory examinations revealed increased white blood cell (WBC) counts(13.97 × 109/L),erythrocyte sedimentation rate (ESR,136 mm/1 h) and C-reactive protein (CRP) level (75 mg/L),decreased hemoglobin level (96 g/L),and high serum levels of IgE (1 596 kU/L),IgG(20.4 g/L)and IgM(6 310 mg/L).Serum immunoelectrophoresis demonstrated that the IgM was a κ-type monoclonal immunoglobulin.Bone marrow examination showed active bone marrow hyperplasia.DNA sequencing analysis of 10 pairs of exons of the NLRP3 gene revealed 3 synonymous mutations,including c.663:C ＞ T:p.T221,c.732:G ＞ A:p.A244A and c.786:A ＞ G:p.R262R.Finally,the patient was diagnosed with Schnitzler's syndrome.There was no improvement of symptoms after the treatment with multiple oral antihistamines at increased dose levels.Then,the treatment protocol was adjusted to oral ciclosporin at a dosage of 200 mg/d for consecutive 18 days,but the patient still showed no response.After the treatment with oral prednisone (30 mg/d) and Tripterygium wilfordii tablets (66 μg thrice a day) for 2 weeks,the skin rashes subsided gradually,and arthralgia was relieved.Moreover,the WBC count,ESR and CRP level were decreased to 9.01 × 109/L,50 mm/1 h and 6 mg/L respectively,while the hemoglobin level was increased to 109.7 g/L.After 1-year follow-up,the dosage of glucocorticoids was gradually decreased to 8 mg/d.In addition,his condition was controlled well with no skin lesions and fever,except for occasional arthralgia in the knees and hip.
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Objective To evaluate the recognition and uptake of transglutaminase 3 (TG3) by dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) receptors on the membrane surface of DC-SIGN-transfected human embryonic kidney (HEK) 293T cells and monocytederived dendritic cells (MDDCs).Methods The eukaryotic expression vector pGCMV-enhanced green fluorescent protein (EGFP) containing DC-SIGN gene fragments was transfected into HEK293T cells to prepare DC-SIGN-EGFP-HEK293T cells by using liposome transfection method.CD14+ monocytes were isolated from peripheral blood samples by magnetic bead-based negative selection,and then were induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to prepare MDDCs.Laser confocal microscopy and flow cytometry were performed to evaluate the recognition and uptake of TG3 protein by DC-SIGN receptors on the surface of HEK293T cells and MDDCs.MDDCs treated without Alexa Fluor 647 dye-tagged TG3 served as blank control group,and those treated with Alexa Fluor 647 dye alone served as negative control group.Results After co-culture with TG3 for 3 hours,laser confocal microscopy and flow cytometry both showed that TG3 could be recognized by and uptaken through DC-SIGN receptors into HEK293T cells and MDDCs.Flow cytometry also revealed that the binding of TG3 to MDDCs could be partially blocked by DC-SIGN blocking antibodies.Neither the negative control group nor the blank control group showed the recognition and binding of TG3 to HEK293T cells and MDDCs.Conclusion TG3 can serve as a kind of autoantigen to be recognized and bound by DC-SIGN receptors,followed by uptake by dendritic cells.
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Objective To detect the serum level of transglutaminase 2 (TG2)-specific IgE (slgE) in patients with atopic dermatitis (AD),and to analyze its correlation with the disease condition.Methods A total of 77 patients with AD were enrolled into this study,including 44 patients aged ≥ 12 years and 33 patients aged ＜ 12 years.Of the 77 patients,20 were diagnosed with intrinsic AD,which was characterized by the absence of sIgE and total serum IgE values ＜ 150 kU/L,and 49 with extrinsic AD characterized by positive (++) or even strongly positive slgE for more than 1 kind of exogenous allergens,or total serum lgE values ≥ 150 kU/L.[mmunocapture-biotinylated detector enzyme immunoassay was performed to detect the serum level of TG2-sIgE in 77 patients with AD,40 adult patients with psoriasis vulgaris (PV) and 30 healthy adult controls.Clinical data on the AD patients were recorded,including age,disease duration,SCORAD score,blood eosinophil count,levels of total IgE and TG2-sIgE.Results The serum levels of TG2-sIgE in AD patients aged ≥ 12 years,AD patients aged ＜ 12 years,PV patients and healthy controls were 1.02 ± 0.2,1.04 ± 0.044,0.93 ± 0.25 and 0.71 ± 0.13,respectively.Additionally,the serum level of TG2-sIgE significantly differed among AD patients aged ≥ 12 years,PV patients and healthy controls (x2 =37.407,P ＜ 0.001),and was significantly higher in both AD patients aged ≥ 12 years and PV patients than in the healthy controls (t =7.38,4.83,respectively,both P ＜ 0.001).Moreover,the intrinsic AD group showed significantly higher TG2-sIgE levels compared with the extrinsic AD group (1.16 ± 0.03 vs.1.02 ± 0.20,t =2.27,P =0.02).The TG2-sIgE level was uncorrelated with the patients' age,disease duration,SCORAD score,blood eosinophil count or serum total IgE levels in AD patients (r =0.03,0.14,-0.04,-0.08,0.06,respectively,all P ＞ 0.05).Conclusion The serum level of TG2-sIgE obviously increases in AD patients,so TG2 may be one kind of autoantigen in AD patients,but there is no significant correlation between the TG2-sIgE level and AD severity.
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Objective To analyze the colonization of Candida, Rhodotorula, Penicillium and Aspergillus in skin surfaces of patients with atopic dermatitis, and to assess the relationship between the four common fungal allergens and severity of atopic dermatitis. Methods Fifty patients with atopic dermatitis and 20 healthy controls were enrolled. Scales were scraped from lesional and non?lesional skin of flexural extremities of the patients, as well as from normal skin of the flexural elbow of healthy controls, then were subjected to microscopic examination and culture. Scale specimens were inoculated onto Sabouraud dextrose agar medium and cultured at 25 ℃ in a constant temperature incubator. Subsequently, suspected fungal or yeast?like colonies were collected for pure culture. Finally, fungal strains were identified according to colony morphology, color, growth speed, as well as microscopic features of spores and hyphae. Results No hyphae or pseudohyphae were found in any case by microscopic examination. Candida albicans and Rhodotorula were detected in 29(58%)and 17(34%)out of the 50 patients, respectively, and in 5(25%)and 2 (10%) out of the 20 healthy controls, respectively. The detection rates of Candida albicans and Rhodotorula were significantly higher in the patients than in the controls(χ2=6.23, 4.10, respectively, both P<0.05). Of 25 patients with severe lesions, 19(76%)and 12(48%)were colonized by Candida albicans and Rhodotorula respectively;among 25 patients with moderate lesions, 10 (40%) and 5 (20%) were colonized by Candida albicans and Rhodotorula respectively. An increase was observed in the detection rates of Candida albicans and Rhodotorula in the patients with severe lesions compared with those with moderate lesions(χ2=6.65, 4.37, respectively, both P<0.05). There was no significant difference in the detection rate of Penicillium or Aspergillus between the patients and health controls. Conclusion The colonization rates of Candida albicans and Rhodotorula on skin surfaces were higher in patients with atopic dermatitis than in healthy controls, and higher in patients with severe lesions than in patients with moderate lesions, indicating that the types of colonizing fungi are associated with the health status of skin and severity of symptoms in patients with atopic dermatitis.
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Objective To analyze γ?secretase gene mutations in a pedigree with acne inversa. Methods Clinical data were collected from a pedigree with acne inversa, which contained 30 members spanning 4 generations. Of these members, 12 were affected by acne inversa, and 9 of the affected members were alive. Peripheral blood DNA was obtained from the proband, his seven relatives (including 4 affected and 3 unaffected members), and 100 unrelatedhealthy human controls. PCR was performed to amplify all the coding exons and their flanking sequences of the NCSTN, PSEN1, PSENEN, Aph1 genes followed by DNA sequencing. Results A heterozygous insertion mutation (c.229_230insCACC)of the PSENEN gene, which led to translational frameshifting and resulted in dysfunciton of the PSENEN protein, was detected in all the 5 patients, but not in unaffected members or healthy controls. Conclusion There is a novel heterozygous insertion mutation c.229_230insCACC in the PSENEN gene, which may be the molecular basis of acne inversa in this family.
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Skin microbiome maintain homeostasis with the host, and affect skin barrier and immune function. The components of skin microbiome are diverse and specific, and are affected by multiple factors. The predominance of Staphylococcus aureus and decrease in diversity of skin microbiome are a characteristic of atopic dermatitis. The overgrowth of S. aureus can aggravate inflammatory reactions in AD. S. epidermidis, although another predominant bacterium in AD, exerts an immunoprotective role by regulating skin barrier?associated immunoreactions through the dendritic cells, interleukin (IL)?17A?producing Th17 cells/IL?17 pathway, and by suppressing the overgrowth of S. aureus. Malassezia can induce and aggravate inflammatory reactions in AD through colonization, sensitization, cross reactions, and other mechanisms. Studies on skin probiotics may provide new directions for the treatment of AD.
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There are various kinds of antihypertensive agents with complex chemical structures. Common antihypertensive agents are divided into 5 classes, including diuretics, calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin Ⅱ receptor blockers and β-blockers, and can cause various types of drug eruptions. This review summarizes clinical characteristics, possible pathogenesis, treatment and consequences of antihypertensive agent-induced drug eruptions, including angioedema, and lupus erythematosus-like, psoriasis-like, eczematoid, herpetiform or lichen planus-like drug eruptions, in hope to facilitate their early detection, diagnosis and treatment, and to provide information and ideas for clinical and basic researches into them.
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Objective To evaluate the efficacy and safety of an acne-clearing device in treating acne vulgaris.Methods A bicenter,randomized,single-blinded,placebo-controlled,parallel-group study was conducted.Seventy-three patients with mild to moderate acne vulgaris were enrolled for the trial.Two similar,clinically matched inflammatory papules were selected from each patient,and divided into a test group and a control group to be treated with an acne-clearing device with an output temperature of 46-50 ℃ and a control device without heat source respectively,for three sessions with the interval varying from 1 to 12 hours between the first two sessions and from 18 to 48 hours between the last two sessions.Every treatment lasted three minutes.Lesional color and size were recorded before and on day 1,5 and 14 after the first treatment.Side effects were also recorded for the evaluation of safety.Results Clinical improvement was observed in 66 (90.4％),73 (100.0％) and 72 (98.6％) patients,and marked improvement in 27 (37.0％),64 (87.7％) and 72 (98.6％) patients on day 1,5 and 14 after the first treatment,respectively.Significant differences existed between the control and test group in improvement rate on day 1 and 5,and in marked improvement rate on all the three time points (all P ＜ 0.01).The average time taken for erythematous swelling to begin to subside and time for lesions to completely heal were 19.51 hours and 7.15 days respectively in the test group,significantly shorter than those in the control group by 82.41 hours and 5.07 days respectively.Conclusions The acne-clearing device proves to be effective and safe for the treatment of mild to moderate acne vulgaris,which can rapidly relieve the inflammation in acne,shorten the time required for erythematous swelling to subside and for lesions to completely heal.