BTK ELISA Kit

X-linked agammaglobulinemia (XLA) is a rare form of inherited immunodeficiency due to an impairment in B-lymphocyte differentiation and maturation. In the majority of cases XLA is diagnosed in childhood, particularly among males affected by recurrent infections and with a family history of immunodeficiency. Infections of respiratory tract, gastrointestinal apparatus, eyes, nose and ears are frequent in XLA patients; on the contrary, infections of myocardium, cardiac valves and pericardium are rarely described in XLA. A 34-year-old man with unknown XLA was hospitalized because of syncope, due to pericardial tamponade, caused by acute primary purulent pericarditis. Immediate pericardiocentesis was effective in improving hemodynamics, and empiric antibiotic therapy was successful in controlling the infection. Purulent pericarditis is a rare disease with high mortality rate: it is usually caused by hematogenous bacterial propagation, direct infection of pericardial space by chest wounds or thoracic surgery, or extension of infection from adjacent tissues. However, this patient had no recent local or systemic infections. Because of unusual clinical picture during hospitalization he underwent further clinical and laboratory evaluations, that showed low immunoglobulin levels. After exclusion of acquired immunodeficiency, genetic tests were performed: they detected deletion of exons 8-9-10 of Bruton Tyrosine Kinase gene on X chromosome, leading to the diagnosis of XLA. Acute purulent primary pericarditis may also occur in adult XLA patients as first clinical manifestation. According to this case report, a primary immunodeficiency syndrome should be considered in patients with atypical cardiac infections and no predisposing conditions, regardless of age.

Ibrutinib (IBN), a first-in-class BTK-inhibitor, was approved by the FDA for the treatment of mantle cell lymphoma (MCL). Although IBN shows excellent performance as an anti-lymphoma agent, it has some undesirable side effects due to its off-target activities. Our studies yielded a novel series of 3-(6-phenoxypyridin-3-yl)-4-amine-1H-pyrazolo [3,4-d]pyrimidine derivatives capable of potent inhibition of Bruton's tyrosine kinase (BTK). Notably, compound 13e explained potent BTK inhibitory activity and could completely inhibit the phosphorylation of BTK and PLC gamma 2 in Z138 cells at low micromolar concentration. Compared with IBN, compound 13e improved anti-proliferative activities 3-40 folds in MCL cell lines with IC50 values lower than 1 mu M. Low micromolar doses of 13e could induce strong cell apoptosis in Jeko-1 and Z138 cells. In addition, compound 13e showed greater BTK selectivity and higher stability in human liver microsomes than IBN and potential safety improvement for the treatment of MCL.