Anti-tumor necrosis factor therapy in patients with difficult-to-treat lupus nephritis: a prospective series of nine patients.

OBJECTIVE: To clarify the efficacy and safety of anti-TNF-alpha therapy for intractable lupus nephritis. METHODS: In nine patients with systemic erythematosus who presented with lupus nephritis resistant to steroids and immunosuppressants, 200 mg/body of infliximab was drip-infused three times. No changes were made to other treatments for three months after the start of anti-TNF-alpha therapy, and urinary findings, renal function, serum complement, anti-DNA antibody, SLE activity, and adverse events were examined for six months after the start of anti-TNF-alpha therapy. RESULTS: One of the nine patients developed pyelonephritis after the first infliximab injection and received no further injections. The remaining eight patients received 3 infliximab injections. Of the eight patients, urinary protein decreased after anti-TNF-alpha therapy in six patients, and the SLEDAI improved in five patients. Urinary findings and/or SLE activity improved in six patients. Of the patients whose urinary protein levels decreased after anti-TNF-alpha therapy, proteinuria recurred six months after anti-TNF-alpha therapy in one patient. After anti-TNF-alpha therapy, proteinuria and the SLEDAI improved significantly. With respect to adverse events, therapy was discontinued in one patient who developed pyelonephritis, and one patient developed decreased blood pressure due to infusion reactions. In one patient in whom the steroid dosage was increased due to poor response to anti-TNF-alpha therapy, brainstem infarction occurred four months later. In one patient, anti-DNA antibody levels increased after therapy, but none of the patients had decreased serum complement levels or increased SLE activity. CONCLUSION: In intractable lupus nephritis, anti-TNF-alpha therapy improved urinary protein levels and SLE activity. Although adverse events must be monitored cautiously, it may be possible to use anti-TNF-alpha therapy as a third-line treatment.

Clonal expansion of T cells infiltrating in the airways of non-atopic asthmatics.

CD4+ T cells are thought to play an important role in airway inflammation in both atopic and non-atopic asthma. However, the mechanism by which T cells are activated in non-atopic asthma, where there is no causative antigen identified, is unknown. To elucidate this issue, we analysed T cell receptor (TCR) Vbeta gene clonotypes of T cells in the bronchoalveolar lavage fluids (BALF) of non-atopic asthmatics using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and a sequencing method. We found that the numbers of TCR Vbeta gene clonotypes of T cells in the BALF of non-atopic asthmatics were significantly increased compared with those of peripheral blood lymphocytes (PBL). We also found that there were several shared amino acid motifs in complementarity-determining region 3 (CDR3) of TCR Vbeta genes from those T cell clones in BALF of non-atopic asthmatics, whereas these shared motifs were not found in the same Vbeta family genes from PBL in the patients. Moreover, a conserved amino acid sequence was detected in two patients who shared a common HLA-DR allele. These results indicate that the infiltrating T cells in the airways of non-atopic asthmatics recognize relatively limited epitopes of antigens and are clonally expanded by antigen-driven stimulation.

Effect of a selective thromboxane A2 receptor antagonist BAY u3405 on antigen-, leukotriene C4- and leukotriene D4-induced bronchoconstriction in guinea pigs.

We studied the effect of a selective thromboxane (TX) A2 receptor antagonist BAY u3405 on prostanoid-, leukotriene (LT) C4, LTD4- and antigen-induced bronchoconstriction in nonanesthetized guinea pigs in vivo. Oral administration of BAY u3405 inhibited bronchoconstriction induced by inhaled TXA2 mimetic U46619, prostaglandin (PG) D2 and PGF2 alpha. BAY u3405 also decreased the bronchoconstriction induced by inhaled LTC4 and LTD4. Intraperitoneal administration of TXA2 synthetase inhibitor OKY-046 did not affect PGD2- and PGF2 alpha-induced bronchoconstriction, but attenuated LTC4- and LTD4-induced bronchoconstriction. BAY u3405 and OKY-046 decreased antigen-induced bronchoconstriction in actively sensitized guinea pigs. These results indicate that BAY u3405 not only inhibits TXA2-, PGD2- and PGF2 alpha-induced bronchoconstriction that is mediated through a TXA2 receptor but also decreases LTC4. LTD4- and antigen-induced bronchoconstriction which is mediated in part through TXA2 synthesis. These results suggest that BAY u3405 might be useful in controlling prostanoid-induced bronchoconstriction in asthma.

[Thrombotic thrombocytopenic purpura (TTP) observed in a patient with primary antiphospholipid antibody syndrome].

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology and has a high mortality rate. TTP is characterized by a pentad of clinical findings, including microangiopathic hemolytic anemia, thrombocytopenia, renal abnormalities, neurologic signs and fever. The pathological feature of TTP consists of disseminated microvascular platelet thrombi. We describe a case of TTP with primary anti-phospholipid syndrome. A 27-year-old woman developed TTP in her second trimester of pregnancy. She presented with classical symptoms of TTP with compatible renal biopsy findings. Although four articles of SLE criteria (1982 ARA) were fulfilled, three of them were considered to be derived from multiple thrombosis except for a positive antinuclear antibody. Positive antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody) with SLE-like findings suggested the diagnosis of antiphospholipid antibody syndrome rather than SLE. Although TTP has been described in patients with SLE and they can share common clinical and pathological features, the relationship between these two diseases is controversial. Many theories have been proposed to explain the nature and cause of intravascular platelet aggregation in TTP. But the pathogenesis of TTP is still unclear. This case suggests an important causal relationship between antiphospholipid antibodies and TTP during pregnancy. In TTP patients who also have SLE or SLE-like features, the antiphospholipid antibodies may have a role in the development of multiple microthrombosis.