Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily.

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

[Myasthenia gravis. Register of 190 cases in a single center]. / Miastenia gravis. Registro de 190 casos en un centro único.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. The aim of this study was to evaluate clinical, epidemiological and serological features of patients with MG in a Public Hospital of Buenos Aires City. A retrospective analysis of 190 patients diagnosed with MG was performed. The mean age of MG onset was 38 years, 30% had late-onset MG (onset age > 50 years). The female/male ratio was 1.7 / 1. Disease started earlier in women than in men, mean 32 vs. 48 years (p < 0.0001). Familial autoimmune MG represented 3.2% of the cases. Most of the patients initiated their disease with a pure ocular form (52%). 12.1% (23/190) were considered ocular MG at follow-up. Thymoma-associated MG represented 11.6% of cases. 27.1% had other associated autoimmune disease, thyroid disorders were the most frequent. 81.4% were anti-acetylcholine receptor antibody (AChR-ab) positive MG; 22.7% of AChR-ab negatives were positive for anti-muscle specific kinase (MusK) antibodies. Clinical outcome was relatively good; more than half of cases were in remission or minimal manifestations at the last visit. The majority of patients required immunosuppression to control the symptoms, 78% received corticosteroids and 48%, a non-steroidal immunosuppressant.

La miastenia gravis (MG) es una enfermedad autoinmune mediada por anticuerpos dirigidos contra proteínas post sinápticas de la unión neuromuscular. El objetivo de este estudio fue describir los aspectos clínicos, epidemiológicos y serológicos de pacientes con MG en un Hospital Público de la Ciudad de Buenos Aires. Se realizó un análisis retrospectivo sobre 190 enfermos con diagnóstico de MG. La edad media de inicio de la enfermedad fue de 38 años; 57 (30%) fueron MG de inicio tardío (inicio de síntomas > 50 años). La relación mujer/hombre fue 1.7/1. La enfermedad se inició más tempranamente en las mujeres que en los hombres, media 32 vs. 48 años (p < 0.0001). La MG familiar autoinmune representó el 3.2 % (6 casos). La forma más común de presentación fue con manifestaciones oculares puras (52%). El 12.1% (23/190) fue considerada MG ocular en el seguimiento. La MG asociada a timoma se presentó en 22 casos (11.6%). El 27.1% presentó otra enfermedad autoinmune asociada, siendo las tiroideas las más frecuentes. El 81.4% tuvo anticuerpos antireceptores de acetilcolina (ACRA) positivos y 22.7% de los ACRA negativos fueron positivos para anticuerpos anti-tirosina quinasa musculo especifica (anti-MusK). La evolución clínica fue favorable, hallándose más de la mitad de los casos en remisión o manifestaciones mínimas en la última visita. La mayoría requirió inmunosupresión para control de la sintomatología, el 78% recibió corticoides y el 48% un inmunosupresor no esteroideo.

Miastenia gravis: Registro de 190 casos en un centro único / Myasthenia gravis. Register of 190 cases in a single center

La miastenia gravis (MG) es una enfermedad autoinmune mediada por anticuerpos dirigidos contra proteínas post sinápticas de la unión neuromuscular. El objetivo de este estudio fue describir los aspectos clínicos, epidemiológicos y serológicos de pacientes con MG en un Hospital Público de la Ciudad de Buenos Aires. Se realizó un análisis retrospectivo sobre 190 enfermos con diagnóstico de MG. La edad media de inicio de la enfermedad fue de 38 años; 57 (30%) fueron MG de inicio tardío (inicio de síntomas > 50 años). La relación mujer/hombre fue 1.7/1. La enfermedad se inició más tempranamente en las mujeres que en los hombres, media 32 vs. 48 años (p < 0.0001). La MG familiar autoinmune representó el 3.2 % (6 casos). La forma más común de presentación fue con manifestaciones oculares puras (52%). El 12.1% (23/190) fue considerada MG ocular en el seguimiento. La MG asociada a timoma se presentó en 22 casos (11.6%). El 27.1% presentó otra enfermedad autoinmune asociada, siendo las tiroideas las más frecuentes. El 81.4% tuvo anticuerpos anti-receptores de acetilcolina (ACRA) positivos y 22.7% de los ACRA negativos fueron positivos para anticuerpos anti-tirosina quinasa musculo especifica (anti-MusK). La evolución clínica fue favorable, hallándose más de la mitad de los casos en remisión o manifestaciones mínimas en la última visita. La mayoría requirió inmunosupresión para control de la sintomatología, el 78% recibió corticoides y el 48% un inmunosupresor no esteroideo.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. The aim of this study was to evaluate clinical, epidemiological and serological features of patients with MG in a Public Hospital of Buenos Aires City. A retrospective analysis of 190 patients diagnosed with MG was performed. The mean age of MG onset was 38 years, 30% had late-onset MG (onset age > 50 years). The female/male ratio was 1.7 / 1. Disease started earlier in women than in men, mean 32 vs. 48 years (p < 0.0001). Familial autoimmune MG represented 3.2% of the cases. Most of the patients initiated their disease with a pure ocular form (52%). 12.1% (23/190) were considered ocular MG at follow-up. Thymoma-associated MG represented 11.6% of cases. 27.1% had other associated autoimmune disease, thyroid disorders were the most frequent. 81.4% were anti-acetylcholine receptor antibody (AChR-ab) positive MG; 22.7% of AChR-ab negatives were positive for anti-muscle specific kinase (MusK) antibodies. Clinical outcome was relatively good; more than half of cases were in remission or minimal manifestations at the last visit. The majority of patients required immunosuppression to control the symptoms, 78% received corticosteroids and 48%, a non-steroidal immunosuppressant.

What is in the Neuromuscular Junction Literature?

This update begins with myasthenia gravis and the roles of anti-agrin and cortactin antibodies. Regarding diagnosis, a report on repeated ice pack testing is highlighted as are several reports on the close correlation of electrodiagnostic testing with clinical features and the response to treatment. The incidence of head drop and associated clinical and ventilatory features are gleaned from a retrospective study. We also discuss a study that assessed the predominantly symmetric and conjugate ocular findings in MuSK-myasthenia gravis. Other topics that are covered include quality of life and preoperative risk. We then summarize the positive treatment trials of subcutaneous immunoglobulin and eculizumab. Turning to Lambert-Eaton Myasthenic Syndrome, we report on an epidemiologic study performed on the veteran affairs population, the results of the DAPPER study of 3, 4 diaminopyridine, and look to the future for other treatment options involving calcium gating modifiers.

Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors.

OBJECTIVE: The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters. STUDY DESIGN: We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed. RESULTS: Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001). CONCLUSIONS: The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.

Anaplastic lymphoma kinase-positive large B-cell lymphoma: a case report with particular immunophenotypic features.

Anaplastic lymphoma kinase-positive large B-cell lymphoma is a rare and aggressive B-cell lymphoma mostly associated with t(2:17) involving the clathrin gene at 17q23 and the anaplastic lymphoma kinase gene at 2p23. The characteristic immunophenotype includes a granular cytoplasmic anaplastic lymphoma kinase expression, CD20 negativity and the presence of plasma cell markers (CD138, VS38c, and CD38). We report a case with aberrant immunophenotype (CD138-, VS38c-, CD38+/-) and discuss the utility of other immunohistochemical markers in establishing a terminal B-cell differentiation.

"Seronegative" anti-MUSK positive myasthenia gravis presenting during pregnancy.

Myasthenia gravis is an autoimmune disease characterized by weakness and fatigue of the skeletal muscles of the face and extremities. Pregnancy is associated with 19-41% of exacerbations. We present a 19-year-old woman who was seen at the neurology clinic 10 days after her last cesarean section with diplopia and trouble swallowing liquids and solids for the previous 3 months. On examination she had slurred speech, bilateral palpebral ptosis, and mild droop of her shoulders. An arterial blood sample showed a PCO2 of 50 mmHg and a PO2 of 70 mmHg. The tensilon test was positive, Intravenous methylprednisolone and immunoglobulin and oral pyridostigmine effectively relieved her myasthenic signs and symptoms. Five assays for acetylcholine or anti-striational antibodies in her serum were negative. A test for muscle-specific tyrosine kinase antibody was positive. In 10-20% of patients with myasthenia gravis no antibodies to acetylcholine receptors are detectable. Forty percent of this group has an antibody to muscle-specific tyrosine kinase.