Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte.

The Tec protein tyrosine kinase (PTK) belongs to a group of structurally related nonreceptor PTKs that also includes Btk, Itk, Rlk, and Bmx. Previous studies have suggested that these kinases play important roles in hematopoiesis and in the lymphocyte signaling pathway. Despite evidence suggesting the involvement of Tec in the T-lymphocyte activation pathway via T-cell receptor (TCR) and CD28, Tec's role in T-lymphocytes remains unclear because of the lack of apparent defects in T-lymphocyte function in Tec-deficient mice. In this study, we investigated the role of Tec in human T-lymphocyte using the Jurkat T-lymphoid cell line stably transfected with a cDNA encoding Tec. We found that the expression of wild-type Tec inhibited the expression of CD25 induced by TCR cross-linking. Second, we observed that LFM-A13, a selective inhibitor of Tec family PTK, rescued the suppression of TCR-induced CD25 expression observed in wild-type Tec-expressing Jurkat cells. In addition, expression of kinase-deleted Tec did not alter the expression level of CD25 after TCR ligation. We conclude that Tec PTK mediates signals that negatively regulate CD25 expression induced by TCR cross-linking. This, in turn, implies that this PTK plays a role in the attenuation of IL-2 activity in human T-lymphocytes.

F-18 FDG PET findings of Takayasu arteritis before and after immunosuppressive therapy.

A 73-year-old woman with a 3-month history of fever of unknown origin underwent F-18 FDG positron emission tomography (PET). The serum C-reactive protein was 9.62 mg/dL. Her systolic blood pressure was 120 and 96 mm Hg in the right and left arms, respectively. FDG PET images demonstrated intense FDG uptake in the aorta and bilateral subclavian and brachiocephalic arteries consistent with Takayasu arteritis. After 6 weeks of immunosuppressive therapy, a follow-up PET scan showed disappearance of the large vessel uptake of FDG. She was asymptomatic, with a normal C-reactive protein (0.06 mg/dL).

A case of rheumatoid arthritis complicated by demyelination in both cerebral cortex and spinal cord during etanercept therapy.

Tumor necrosis factor (TNF) antagonists, including etanercept, have been approved for the treatment of rheumatoid arthritis (RA). These agents are not free of adverse events like other antirheumatic agents. Several important adverse events in CNS lesions have been reported. In this paper, we report on one patient with RA that had complications from a demyelinating disorder during TNF-blockade therapy using etanercept at 24 months after initial administration. A 66-year-old Japanese woman was diagnosed with RA in 1959. She received various disease-modifying antirheumatic drugs (DMARDs), but all of these agents were ineffective. She was administered etanercept in June 2005, and stayed well. Twenty-four months after the initial administration of etanercept, she developed palsy of bilateral upper extremities and gait disturbance subacutely, and was then admitted to our institute in August 2007. MRI of her spinal cord revealed a high-intensity lesion from the third through to the seventh cervical (C3-C7) levels. Additionally, T2-weighted MRI images showed disseminated high-intensity lesions in the white matter of brain. She was suspected of having a demyelinating disorder based on these MRI findings. There was no significant finding that pointed to another neurological disorder. High-dose corticosteroid therapy was conducted and was effective for her.

Two cases of refractory thrombotic thrombocytopenic purpura associated with collagen vascular disease were significantly improved by rituximab treatment.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels. TTP is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, and its inhibitor. Low ADAMTS13 activity is present in most of idiopathic TTP patients. The prognosis of TTP was improved by plasma exchange treatment, which replaces the ADAMTS13 and removes ADAMTS13 inhibitor. However, ADAMTS13 activity is normal in some TTP patients. These are found among the secondary TTP patients associated with collagen disease, hematopoietic stem cell transplantation, malignancy, or drugs. In addition, most of them do not respond to plasma exchange. On the other hand, several reports demonstrated that rituximab, which is an anti-CD20 monoclonal antibody, is effective for refractory TTP cases caused by ADAMTS13 deficiency. It is considered that the effect of rituximab is associated with disappearance of ADAMTS13 inhibitor. However, rituximab therapy was effective for the TTP patients with normal ADAMTS13 activity in our cases. We considered another mechanism of rituximab for TTP cases.