BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associat...BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associated with several skin diseases,including atopic dermatitis(AD).The treatment of LA is considered to be difficult.However,as there is some overlap in the etiopathogenesis of LA and AD,AD treatment may also be effective for LA.CASE SUMMARY Case 1:A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs.He had a long history of the disease(8 years),with repeated and polymorphic skin lesions.Given the poor efficacy of traditional treatments,this patient was recommended to receive dupilumab treatment.At the initial stage,300 mg was injected subcutaneously every 2 wk.After 28 wk,the drug interval was extended to 1 mo due to the pandemic.Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90(skin lesions improved by 90%compared with the baseline)by the end of the study.Moreover,Investigator's Global Assessment score was 1,and scoring atopic dermatitis index and numeric rating scale improved by 97.7%and 87.5%compared with the baseline,respectively,with LA skin lesions having largely subsided.Case 2:A 30-year-old woman was diagnosed with severe AD with LA,due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis,and erythema and papules scattered on limbs and trunk with pruritus,present for 25 years.After 16 wk of dupilumab treatment,she stopped,and skin lesions completely subsided,without recurrence since the last follow-up.CONCLUSION Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA,in addition to benefits in the quality of life of the patients.展开更多
BACKGROUND Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant(IT), immune active(IA), inactive carrier(IC) and hepatitis B envelope antigen(HBeAg)-negative hepa...BACKGROUND Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant(IT), immune active(IA), inactive carrier(IC) and hepatitis B envelope antigen(HBeAg)-negative hepatitis(ENEG).AIM To investigate the immune status of natural killer(NK) and T cells in different phases of chronic hepatitis B.METHODS The frequency, phenotype and function of circulating NK cells, as well as nonantigen-specific and hepatitis B virus(HBV)-specific T cell responses were detected by flow cytometry in healthy and HBV-infected subjects.RESULTS The ability of NK cells to produce IFN-γ was markedly attenuated in HBVinfected patients overall but was less compromised in IC patients. Patients in the IT and IA phases also displayed significantly lower TNF-α production compared to healthy subjects. NK cells were phenotypically activated in the IA and ENEGphases, as evidenced by the upregulation of NKp44 in CD56^(bright) NK cells and CD69 in CD56^(dim) NK cells. Furthermore, global T-cells from the ENEG phase displayed a proinflammatory cytokine profile with upregulated IFN-γ and TNF-αexpression, while this profile was suppressed in IT and IA patients. Finally, core and S antigen-specific T cell responses were significantly stronger after in vitro expansion in the IC phase compared to other phases.CONCLUSION Our findings demonstrate the changes in immune response pattern during the natural history of HBV infection. Both NK and T cells are functionally impaired in the IT and IA phases. With the spontaneous clearance of HBeAg and hepatitis B surface antigen decline, NK cell cytokine production and HBV-specific T responses are partially restored in IC phase, and the ENEG phase is dominated by nonantigen-specific T cell responses.展开更多
AIM: To investigate the expression of interleukin(IL)-33 in the cornea and human corneal epithelial cells(HCECs) exposed to Aspergillus fumigatus(A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling...AIM: To investigate the expression of interleukin(IL)-33 in the cornea and human corneal epithelial cells(HCECs) exposed to Aspergillus fumigatus(A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection.METHODS: The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction(q RT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase(MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qR T-PCR and enzymelinked immunosorbent assay(ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8(CCK8) assay and cell count.RESULTS: IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection,as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine(IL-6 and IL-1β) production at both the mRNA and protein levels. This production of proinflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 administration for 48 h and 72 h promoted the proliferation of HCECs, which was attenuated by treatment with soluble recombinant human ST2 protein.CONCLUSION: A. fumigatus elevates IL-33 expression in human and mice corneas and HCECs. Thus, IL-33/ST2/p38 signaling may play an important role in amplifying the immune response of corneal epithelial cells to A. fumigatus infection. Besides, IL-33 promotes the cell proliferation of HCECs via its receptor ST2. These findings suggest a novel autocrine mechanism of amplification of the fungalinduced inflammatory response in the corneal epithelium, highlighting a potential therapeutic target for fungal keratitis.展开更多
BACKGROUND Lichen planus(LP)with distribution of lesions along Blaschko’s lines is a rare entity,accounting for 0.24%-0.62%of all patients.Unilateral distribution of lesions in arm,leg,trunk,and waist is even less co...BACKGROUND Lichen planus(LP)with distribution of lesions along Blaschko’s lines is a rare entity,accounting for 0.24%-0.62%of all patients.Unilateral distribution of lesions in arm,leg,trunk,and waist is even less common.Approximately 10%of patients with LP manifest nail lesions.CASE SUMMARY A 20-year-old woman presented to our department with polygonal,purpuric,flattopped papules over the right arm,right leg,and right side of trunk and waist for the last 5 mo.The patient initially developed nail deformation in the left middle finger with no obvious cause,followed by development of blue-purple and red maculopapular rash with pruritus.During the disease course,the skin lesions aggravated and spread to several segments due to scratching.The lesions showed unilateral distribution along the Blaschko’s lines.The diagnosis of LP along Blaschko’s lines was established based on dermoscopy and skin biopsy.Her cutaneous lesions considerably improved after 4-wk treatment with intramuscular glucocorticoid,oral acitretin,topical glucocorticoid,and retinoids.CONCLUSION Cases of LP involving multiple segments of the body along the Blaschko’s lines with nail damage are rare.展开更多
基金Supported by National Natural Science Foundation of China,No.81803160Scientific Development Program of Jilin Province,No.20200801078GH.
文摘BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associated with several skin diseases,including atopic dermatitis(AD).The treatment of LA is considered to be difficult.However,as there is some overlap in the etiopathogenesis of LA and AD,AD treatment may also be effective for LA.CASE SUMMARY Case 1:A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs.He had a long history of the disease(8 years),with repeated and polymorphic skin lesions.Given the poor efficacy of traditional treatments,this patient was recommended to receive dupilumab treatment.At the initial stage,300 mg was injected subcutaneously every 2 wk.After 28 wk,the drug interval was extended to 1 mo due to the pandemic.Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90(skin lesions improved by 90%compared with the baseline)by the end of the study.Moreover,Investigator's Global Assessment score was 1,and scoring atopic dermatitis index and numeric rating scale improved by 97.7%and 87.5%compared with the baseline,respectively,with LA skin lesions having largely subsided.Case 2:A 30-year-old woman was diagnosed with severe AD with LA,due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis,and erythema and papules scattered on limbs and trunk with pruritus,present for 25 years.After 16 wk of dupilumab treatment,she stopped,and skin lesions completely subsided,without recurrence since the last follow-up.CONCLUSION Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA,in addition to benefits in the quality of life of the patients.
基金Supported by National Science Fund of China(NSFC)No.30771911National Science and Technology Major Project No.2012ZX10002007-003
文摘BACKGROUND Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant(IT), immune active(IA), inactive carrier(IC) and hepatitis B envelope antigen(HBeAg)-negative hepatitis(ENEG).AIM To investigate the immune status of natural killer(NK) and T cells in different phases of chronic hepatitis B.METHODS The frequency, phenotype and function of circulating NK cells, as well as nonantigen-specific and hepatitis B virus(HBV)-specific T cell responses were detected by flow cytometry in healthy and HBV-infected subjects.RESULTS The ability of NK cells to produce IFN-γ was markedly attenuated in HBVinfected patients overall but was less compromised in IC patients. Patients in the IT and IA phases also displayed significantly lower TNF-α production compared to healthy subjects. NK cells were phenotypically activated in the IA and ENEGphases, as evidenced by the upregulation of NKp44 in CD56^(bright) NK cells and CD69 in CD56^(dim) NK cells. Furthermore, global T-cells from the ENEG phase displayed a proinflammatory cytokine profile with upregulated IFN-γ and TNF-αexpression, while this profile was suppressed in IT and IA patients. Finally, core and S antigen-specific T cell responses were significantly stronger after in vitro expansion in the IC phase compared to other phases.CONCLUSION Our findings demonstrate the changes in immune response pattern during the natural history of HBV infection. Both NK and T cells are functionally impaired in the IT and IA phases. With the spontaneous clearance of HBeAg and hepatitis B surface antigen decline, NK cell cytokine production and HBV-specific T responses are partially restored in IC phase, and the ENEG phase is dominated by nonantigen-specific T cell responses.
基金Supported by the National Natural Science Foundation of China(No.81470609 No.81700800+5 种基金 No.81870632 No.81800800)Natural Science Foundation of Shandong Province(No.ZR2013HQ007 No.ZR2017MH008 No.ZR2017BH025)the Youth National Natural Science Foundation of China(No.81500695)
文摘AIM: To investigate the expression of interleukin(IL)-33 in the cornea and human corneal epithelial cells(HCECs) exposed to Aspergillus fumigatus(A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection.METHODS: The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction(q RT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase(MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qR T-PCR and enzymelinked immunosorbent assay(ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8(CCK8) assay and cell count.RESULTS: IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection,as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine(IL-6 and IL-1β) production at both the mRNA and protein levels. This production of proinflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 administration for 48 h and 72 h promoted the proliferation of HCECs, which was attenuated by treatment with soluble recombinant human ST2 protein.CONCLUSION: A. fumigatus elevates IL-33 expression in human and mice corneas and HCECs. Thus, IL-33/ST2/p38 signaling may play an important role in amplifying the immune response of corneal epithelial cells to A. fumigatus infection. Besides, IL-33 promotes the cell proliferation of HCECs via its receptor ST2. These findings suggest a novel autocrine mechanism of amplification of the fungalinduced inflammatory response in the corneal epithelium, highlighting a potential therapeutic target for fungal keratitis.
基金Supported by National Natural Science Foundation of China,No.81803160.
文摘BACKGROUND Lichen planus(LP)with distribution of lesions along Blaschko’s lines is a rare entity,accounting for 0.24%-0.62%of all patients.Unilateral distribution of lesions in arm,leg,trunk,and waist is even less common.Approximately 10%of patients with LP manifest nail lesions.CASE SUMMARY A 20-year-old woman presented to our department with polygonal,purpuric,flattopped papules over the right arm,right leg,and right side of trunk and waist for the last 5 mo.The patient initially developed nail deformation in the left middle finger with no obvious cause,followed by development of blue-purple and red maculopapular rash with pruritus.During the disease course,the skin lesions aggravated and spread to several segments due to scratching.The lesions showed unilateral distribution along the Blaschko’s lines.The diagnosis of LP along Blaschko’s lines was established based on dermoscopy and skin biopsy.Her cutaneous lesions considerably improved after 4-wk treatment with intramuscular glucocorticoid,oral acitretin,topical glucocorticoid,and retinoids.CONCLUSION Cases of LP involving multiple segments of the body along the Blaschko’s lines with nail damage are rare.