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1.
Public Health ; 223: 94-101, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37625273

RESUMO

OBJECTIVES: Angola has a high burden of unregistered children and efforts to increase birth-registration coverage have not yielded the desired progress. This study aimed to examine sociodemographic and healthcare-related factors associated with birth registration in Angola. STUDY DESIGN: Secondary data analysis of the Maternal and Child Health (MCH) Handbook randomised controlled trial conducted in Benguela province, Angola and involving 11,006 women. METHODS: For this analysis, we excluded women with missing data on birth registration (n = 1424), multiple gestation (n = 243), and those with infant death (n = 6). The final study population included 9333 women with infants under one year of age. We used multilevel mixed-effects logistic regression analysis to determine sociodemographic and healthcare-related factors associated with the registration of a child's birth. RESULTS: Of the 9333 live births, 25% (95% confidence interval [CI] = 13.4-41.8) were registered, while 21% (95%CI = 11.1-35.7) were registered with certificate. There were higher proportions of registered births among mothers who possessed the MCH Handbook across various demographic and healthcare indicators. Birth registration was most significantly associated with facility-based delivery (odds ratio [OR] = 2.97; 95%CI = 2.45-3.61), possession of MCH Handbook (OR = 2.04; 95%CI = 1.70-2.46), and complete scheduled vaccination visits (OR = 1.69; 95%CI = 1.44-1.97). Higher maternal age and education level, belonging to the highest wealth quintile, beginning antenatal care in the first trimester, attending at least four antenatal care visits, and using postnatal care services were positively associated with registration of birth. CONCLUSION: Maternal healthcare factors showed significant associations with birth registration and integrating birth-registration processes with certain maternal and child health services may further raise awareness and boost registration levels in Angola.


Assuntos
Serviços de Saúde Materna , Lactente , Criança , Humanos , Feminino , Gravidez , Angola/epidemiologia , Cuidado Pré-Natal , Mães , Atenção à Saúde
2.
Br J Dermatol ; 180(4): 881-887, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30120913

RESUMO

BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1ß is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. OBJECTIVES: To evaluate the clinical features of seven cases with anti-TIF-1ß antibodies alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1ß. RESULTS: Anti-TIF-1ß antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1ß antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were confirmed to have anti-TIF-1ß antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1ß antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.


Assuntos
Autoanticorpos/imunologia , Dermatomiosite/imunologia , Proteína 28 com Motivo Tripartido/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/isolamento & purificação , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Feminino , Humanos , Imunoprecipitação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
J Wound Care ; 26(4): 179-183, 2017 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-28379097

RESUMO

OBJECTIVE: The aim of this study was to examine the accuracy of visual diagnosis of tinea pedis (Athlete's foot) and tinea unguium (fungal nail infection), as well as to provide information on skin abnormalities that could help identify these diseases in aged care facilities (long-term care facilities (LTCFs) and nursing homes). METHOD: A multicentre, cross-sectional observational study was conducted in a LTCF and two nursing homes. A dermatologist observed the skin abnormalities in the participants' interdigital and plantar areas, to screen for tinea pedis, and in the participants' toenails, to screen for tinea unguium. If abnormalities were noted, samples such as scales or toenails were collected and examined using direct microscopy. The accuracy of the macroscopic observation for each skin abnormality was examined. RESULTS: A total of 173 residents were recruited. The accuracy of clinical diagnosis using macroscopic observation was relatively low. The sensitivities and specificities for clinical diagnosis were 0.37 and 0.95 for tinea pedis in the interdigital areas, 0.47 and 0.94 for tinea pedis in the plantar areas, and 0.80 and 0.61 for tinea unguium in toenails, respectively. Scales in the plantar areas and discoloration of the toenails were more frequently observed in residents with tinea pedis and tinea unguium than in those without them. CONCLUSION: Several skin abnormalities were observed in the residents recruited in this study, but there was insufficient correlation with tinea pedis and tinea unguium to be used for screening.


Assuntos
Instituição de Longa Permanência para Idosos , Casas de Saúde , Onicomicose/diagnóstico , Tinha dos Pés/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dermatologistas , Feminino , Humanos , Masculino , Unhas/patologia , Onicomicose/patologia , Reconhecimento Visual de Modelos , Sensibilidade e Especificidade , Pele/patologia , Tinha dos Pés/patologia
5.
Cancer Gene Ther ; 24(2): 45-47, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28106046

RESUMO

We previously described the development of a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of MDA-MB-231 human breast cancer in nude mice. The isolated variant is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared with 2 of 12 of the parental cell line. OBP-401 is a telomerase-dependent cancer-specific, green fluorescent protein (GFP)-expressing adenovirus. OBP-401 was used to infect parental MDA-MB-231P cells and high-metastatic MDA-MB-231H and MDA-MB-231HLN isolated from a lymph node metastasis and MDA-MB-231HLM isolated from a lung metastasis. Time-course imaging showed that OBP-401 labeled MDA-MB-231HP, MDA-MB-231HLN, and MDA-MB-231HLM cells more brightly than MDA-MB-231 parental cells. OBP-401 killed MDA-MB-231H, MDA-MB-231HLN, and MDA-MB-231HLM cells more efficiently than MDA-MB-231P parental cells. These results indicate that OBP-401 could infect, label and then kill high-metastatic MDA-MB-231 more efficiently than low-metastatic MDA-MB-231.


Assuntos
Adenoviridae/genética , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Vírus Oncolíticos/genética , Telomerase/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Expressão Gênica , Genes Reporter , Humanos , Camundongos , Metástase Neoplásica , Neoplasias de Mama Triplo Negativas/terapia
6.
Br J Dermatol ; 176(2): 395-402, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27452897

RESUMO

BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.


Assuntos
Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/imunologia , Corticosteroides/uso terapêutico , Autoanticorpos/metabolismo , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
9.
Eur J Gynaecol Oncol ; 35(5): 535-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25423699

RESUMO

Isolated para-arotic lymph node recurrence of endometrial cancer occurs occasionally, but management of such patients has been controversial. The authors performed cytoreductive surgery in four patients with isolated para-aortic lymph node metastasis of recurrent endometrial cancer. They resected metastatic foci by laparoscopic method for three cases and by laparotomy for one case. After the surgery, three cases underwent radiation therapy and one case was given chemotherapy as adjuvant therapy. After the treatment for recurrence, progression-free interval was from 64 to 127 months and all cases had no evidence of disease. Cytoreductive surgery may improve prognosis of isolated para-aortic lymph node metastasis of recurrent endometrial cancer. As laparoscopic surgery is superior to laparotomy in terms of less invasiveness, further examinations will reveal that it is feasible for such an isolated lymph node recurrence situation.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Laparoscopia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
10.
Clin Genet ; 86(4): 383-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24116970

RESUMO

Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by mutations in CDSN and is characterized by superficial peeling of the upper epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes that plays an important role in maintaining epidermis integrity. Herein, we report a patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region encompassing the CDSN gene, which abrogates CDSN expression. Several genes including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted, however, the patient showed only clinical features typical of PSD. The deletion size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that both telomeric and centromeric breakpoints existed within Alu-S sequences that were oriented in opposite directions. These results suggest an Alu-mediated recombination event as the mechanism underlying the deletion in our patient.


Assuntos
Elementos Alu/genética , Dermatite Esfoliativa/genética , Glicoproteínas/genética , Dermatopatias Genéticas/genética , Deleção Cromossômica , Dermatite Esfoliativa/patologia , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Glicoproteínas/biossíntese , Homozigoto , Humanos , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intercelular , Recombinação Genética , Dermatopatias Genéticas/patologia
11.
Br J Dermatol ; 170(2): 328-31, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24117339

RESUMO

BACKGROUND: The direct microscopy, fungal culture and histopathology that are necessary for the definitive diagnosis of tinea unguium are disadvantageous in that detection sensitivity is affected by the level of skill of the person who performs the testing, and the procedures take a long time. OBJECTIVES: The Dermatophyte Test Strip, which was developed recently, can simply and easily detect filamentous fungi in samples in a short time, and there are expectations for its use as a method for tinea unguium screening. With this in mind, we examined the detection capacity of the Dermatophyte Test Strip for tinea unguium. METHODS: The presence or absence of fungal elements was judged by direct microscopy and Dermatophyte Test Strip in 165 nail samples obtained from residents in nursing homes for the elderly. Moreover, the minimum sample amount required for positive determination was estimated using 32 samples that showed positive results by Dermatophyte Test Strip. RESULTS: The Dermatophyte Test Strip showed 98% sensitivity, 78% specificity, 84·8% positive predictive value, 97% negative predictive value and a positive and negative concordance rate of 89·1%. The minimum sample amount required for positive determination was 0·002-0·722 mg. CONCLUSIONS: The Dermatophyte Test Strip showed very high sensitivity and negative predictive value, and was considered a potentially useful method for tinea unguium screening. Positive determination was considered to be possible with a sample amount of about 1 mg.


Assuntos
Tinha/diagnóstico , Humanos , Unhas/microbiologia , Fitas Reagentes , Sensibilidade e Especificidade
12.
Eur J Gynaecol Oncol ; 34(5): 425-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24475576

RESUMO

PURPOSE: The authors conducted this retrospective study to evaluate the efficacy of radiotherapy (RT) for high-risk patients with adenocarcinoma (AC) compared with chemotherapy (CT) after radical hysterectomy. MATERIALS AND METHODS: There were 263 patients with AC and 58 with adenosquamous cell carcinoma (ASCC). Of these 321 patients, 151 received adjuvant treatment. Of these 151 patients, 69 received radiotherapy (RT) alone, including concurrent chemoradiotherapy (CCRT) with weekly cisdiamminedichloroplatinum (CDDP), 64 patients received CT alone, and 18 patients received concomitant RT and CT (RT + CT). RESULTS: The five-year overall survival (OS) was 70.9% for patients receiving RT, 79.2% for CT, and 66.2% for RT + CT. Adjuvant treatment did not affect the incidence or the pattern of recurrence. The incidence of lymph node involvement was 9.0% in Stage Ib1, 23.9% in Stage Ib2, 30.8% in Stage IIa, and 41.2% in Stage IIb. CONCLUSIONS: Adjuvant CT may be effective for high-risk patients with cervical adenocarcinoma.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Histerectomia , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
13.
J Eur Acad Dermatol Venereol ; 27(7): 867-75, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22646803

RESUMO

BACKGROUND: Although dermokine-ß, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl-terminal domain shares a high pI value with many cytokines, suggesting similar functions. OBJECTIVE: To better understand the biology of dermokine, we here determined its localization under pathological conditions and examined factors that regulate its expression. METHODS: We generated an anti-human dermokine-ß/γ monoclonal antibody cross-reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine-ß/γ were performed with various tissue samples. RESULTS: Although human dermokine-ß/γ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti-dermokine-ß/γ antibody in inflammatory skin disorders. Dermokine-ß/γ was expressed in keratoacanthoma and a part of well-differentiated squamous cell carcinoma (SCC). However, dermokine-ß/γ was not detected in poorly differentiated SCC or tumours derived from non-keratinocytes. In mice, dermokine-ß/γ-expressed keratinocytes were increased in models of contact hypersensitivity, ultraviolet-irradiated skin injury and wound healing. Consistent with expanded distribution in inflammatory skin diseases, proinflammatory cytokines such as interleukin-1ß, interleukin-12, and tumour necrosis factor-α augmented dermokine-ß/γ expression in cultured human keratinocytes. In contrast, growth factors including epidermal growth factor, insulin-like growth factor-I, keratinocyte growth factor and transforming growth factor-α significantly reduced dermokine expression. CONCLUSION: These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.


Assuntos
Proteínas , Dermatopatias/metabolismo , Animais , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos Endogâmicos C57BL , Proteínas/análise , Proteínas/genética , Pele/química , Dermatopatias/genética
14.
Poult Sci ; 91(10): 2444-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22991526

RESUMO

Vaccination of poultry is one promising strategy to mitigate Salmonella infection in poultry and, in turn, humans as well. We evaluated the efficacy of outer membrane protein A (OmpA) as a novel vaccine candidate against Salmonella in poultry. Native OmpA purified from Salmonella enterica serovar Enteritidis was mixed with adjuvant and administered intramuscularly to 41-d-old chicks. The vaccinated birds showed no decrease in cecal excretion and tissue colonization compared with the unvaccinated birds after oral challenge with 10(9) cfu of the homologous strain at 28 d postimmunization. However, this vaccination induced an increased level of serum anti-OmpA IgG. Similar results were obtained in the replication experiments using a recombinant OmpA with single and double doses. For the development of more effective component vaccines for avian salmonellosis, the vaccine efficacy of outer membrane proteins other than OmpA and route of immunization other than parenteral administration should be evaluated with regard to protection and immune responses, including mucosal IgA.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Galinhas , Doenças das Aves Domésticas/prevenção & controle , Salmonelose Animal/prevenção & controle , Salmonella enteritidis/metabolismo , Animais , Imunidade Humoral , Imunização , Doenças das Aves Domésticas/microbiologia , Proteínas Recombinantes/imunologia , Salmonelose Animal/microbiologia
17.
Phys Rev Lett ; 106(3): 034501, 2011 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-21405277

RESUMO

When a drop impacts onto a liquid pool, it ejects a thin horizontal sheet of liquid, which emerges from the neck region connecting the two liquid masses. The leading section of this ejecta bends down to meet the pool liquid. When the sheet touches the pool, at an "elbow," it ruptures and sends off microdroplets by a slingshot mechanism, driven by surface tension. High-speed imaging of the splashing droplets suggests the liquid sheet is of submicron thickness, as thin as 300 nm. Experiments in partial vacuum show that air resistance plays the primary role in bending the sheet. We identify a parameter regime where this slingshot occurs and also present a simple model for the sheet evolution, capable of reproducing the overall shape.

18.
Poult Sci ; 89(8): 1629-34, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20634517

RESUMO

The present study investigated the potential of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) definitive type 104 (DT104) to contaminate eggs in vivo. Of 10 strains of Salmonella Typhimurium DT104, none caused egg contamination when hens were inoculated orally. Three passages of the strains through recovery from the reproductive organs of intravenously infected laying hens resulted in no egg contamination after oral infection of the hens. Feed and water withdrawal for 24 h at 5 and 10 d after oral infection with Salmonella Typhimurium DT104 slightly decreased egg production but did not lead to egg contamination. Finally, oral infection of pullets at the onset of lay (approximately 50% of egg production) resulted in egg contamination (1.7%) in 2 wk. In conclusion, the Salmonella Typhimurium DT104 strains used in the present study have a low possibility of causing egg contamination; however, because infection at the onset of lay can cause egg contamination, the introduction of Salmonella Typhimurium DT104 into the layer houses should be prevented, especially when hens start laying eggs.


Assuntos
Ovos/microbiologia , Doenças das Aves Domésticas/microbiologia , Salmonelose Animal/microbiologia , Salmonella typhimurium , Animais , Galinhas , Feminino , Humanos , Oviposição/fisiologia , Infecções por Salmonella/etiologia , Salmonelose Animal/imunologia , Salmonella typhimurium/isolamento & purificação
19.
Br J Dermatol ; 162(2): 332-6, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19747218

RESUMO

BACKGROUND: Previous studies suggest that CCL13 may have some role in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: To determine serum levels of CCL13 and its clinical associations in patients with SSc. METHODS: Serum CCL13 levels were examined by enzyme-linked immunosorbent assay in 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), 20 patients with dermatomyositis (DM), 29 patients with atopic dermatitis (AD) and 50 healthy individuals. RESULTS: Mean + or - SD serum CCL13 levels were elevated in patients with SSc (81.3 + or - 55.8 pg mL(-1)) compared with healthy controls (15.0 + or - 9.9 pg mL(-1); P < 0.001) and patients with SLE (22.0 + or - 6.9 pg mL(-1); P < 0.001), DM (24.4 + or - 36.1 pg mL(-1); P < 0.001) and AD (18.0 + or - 6.4 pg mL(-1); P < 0.001). Among patients with SSc, there were no differences in serum CCL13 levels between limited cutaneous SSc and diffuse cutaneous SSc. In a longitudinal study, CCL13 levels were generally unchanged during the follow-up. CONCLUSIONS: Serum CCL13 was specifically increased in patients with SSc, but not in patients with SLE, DM or AD or in healthy controls. CCL13 could be a promising serological marker for SSc.


Assuntos
Dermatite Atópica/sangue , Dermatomiosite/sangue , Lúpus Eritematoso Sistêmico/sangue , Proteínas Quimioatraentes de Monócitos/sangue , Escleroderma Sistêmico/sangue , Adulto , Povo Asiático , Biomarcadores/sangue , Estudos de Casos e Controles , Dermatite Atópica/imunologia , Dermatomiosite/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/imunologia , Índice de Gravidade de Doença , Estatística como Assunto , Estatísticas não Paramétricas
20.
Clin Exp Immunol ; 159(2): 176-84, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19919568

RESUMO

Studies have demonstrated that B cells play important roles in systemic sclerosis (SSc), especially through the CD19/CD22 autoimmune loop. CD22 is a B cell-specific inhibitory receptor that dampens B cell antigen receptor (BCR) signalling via tyrosine phosphorylation-dependent mechanism. In this study, we examined the presence and functional property of circulating autoantibodies reacting with CD22 in systemic sclerosis. Serum samples from 10 tight skin (TSK/+) mice and 50 SSc patients were assessed for anti-CD22 autoantibodies by enzyme-linked immunosorbent assays using recombinant mouse or human CD22. The association between anti-CD22 antibodies and clinical features was also investigated in SSc patients. Furthermore, the influence of SSc serum including anti-CD22 autoantibodies for CD22 tyrosine phosphorylation was examined by Western blotting using phosphotyrosine-specific antibodies reacting with four major tyrosine motifs of CD22 cytoplasmic domain. Anti-CD22 autoantibodies were positive in 80% of TSK/+ mice and in 22% of SSc patients. Patients positive for anti-CD22 antibodies showed significantly higher modified Rodnan skin thickness score compared with patients negative for anti-CD22 antibodies. Furthermore, anti-CD22 antibodies from patients' sera were capable of reducing phosphorylation of all four CD22 tyrosine motifs, while sera negative for anti-CD22 antibodies did not affect CD22 phosphorylation. Thus, a subset of SSc patients possessed autoantibodies reacting with a major inhibitory B cell response regulator, CD22. Because these antibodies can interfere CD22-mediated suppression onto B cell activation in vitro, SSc B cells produce functional autoantibodies that can enhance their own activation. This unique regulation may contribute to the autoimmune aspect of SSc.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Escleroderma Sistêmico/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Adulto , Animais , Autoanticorpos/sangue , Linfócitos B/citologia , Linfócitos B/metabolismo , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Fosforilação , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/patologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Tirosina/metabolismo
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