Failure in antigen responses by T cells from patients with common variable immunodeficiency (CVID).

Antigen-driven responses by T cells from patients with CVID and normal subjects have been assessed. Low-density cells enriched for antigen-presenting dendritic cells were cultured with T cells using a 20-microliters hanging drop system. T cells from all subgroups of CVID patients showed markedly reduced responses to the recall antigens purified protein derivative (PPD) or tetanus toxoid, whereas responses by cells from patients with X-linked agammaglobulinaemia, used as a disease control, were in the normal range. However, primary allo-stimulation of CVID T cells was normal. CVID cells from two patients failed to respond to stimulation with a neoantigen, an HIV env peptide, under conditions where normal T cells did respond. These data illustrate a profound defect in antigen-stimulated T cell proliferation in vitro in all groups of CVID patients, but do not distinguish whether the defect is in the presenting cell or in the T lymphocyte. In vivo, germinal centre B cells are thought to present antigen to primed T cells to obtain essential signals (e.g. CD40 ligand and IL-2) for B cell survival and progression to immunoglobulin secretion. A failure of antigen-specific T cell function in vivo in CVID would thus not provide the primed T cells needed for B cell rescue, and could be the primary defect leading to the low immunoglobulin production in this condition.     

A case of antiphospholipid antibody syndrome that manifested in the course of basal cell carcinoma

A case of antiphospholipid antibody syndrome (APS) is presented, which manifested 5 years after onset of basal cell carcinoma (BCC). There were multiple collateral veins due to portal vein thrombosis. Because immunological abnormalities including anti-cardiolipin β₂ glycoprotein-I antibody improved after surgical resection of BCC, it is likely that APS had occurred as a paraneoplastic syndrome with BCC. This case suggests that it is necessary to investigate the presence of APS when BCC is complicated by some coagulopathies.     

Dysregulation of the granulocyte-macrophage colony-stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-gamma, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14+ cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GM-CSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE.     

A case of progressive systemic sclerosis complicated by massive pleural effusion with elevated CA125

A tumor marker, CA125, is known to increase in the serum or other body fluids in various malignancies such as ovarian cancer. Here we present a case of progressive systemic sclerosis (PSS) with massive pleural effusion, in which CA125 in the serum and pleural fluid were elevated. The serum level of CA125 decreased in accordance with the change of the pleural effusion. CA125 level may be an indicator for the activity of serositis in some cases with collagen vascular diseases.     

Signaling through the interleukin-18 receptor α attenuates inflammation in cisplatin-induced acute kidney injury

Interleukin (IL)-18 is produced by leukocytes and renal parenchymal cells (tubular epithelial cells, podocytes, and mesangial cells). The IL-18 receptor (IL-18R) is expressed on these cells in cisplatin-induced acute kidney injury, but the role of IL-18R is unknown. To help define this, we compared IL-18Rα knockout with wild-type mice in cisplatin-induced acute kidney injury and found deteriorated kidney function, tubular damage, increased accumulation of leukocytes (CD4(+) and CD8(+) T-cells, macrophages, and neutrophils), upregulation of early kidney injury biomarkers (serum TNF, urinary IL-18, and KIM-1 levels), and increased expression of pro-inflammatory molecules downstream of IL-18. In vitro, leukocytes from the spleen and kidneys of the knockout mice produced greater amounts of pro-inflammatory cytokines upon stimulation with concanavalin A compared to that in wild-type mice. Levels of the suppressor of cytokine signaling 1 and 3 (negative regulators of cytokine signaling) were reduced in the spleen and kidneys of IL-18Rα-deficient compared to wild-type mice. Adoptive transfer of wild-type splenocytes by IL-18Rα-deficient mice led to decreased cisplatin nephrotoxicity compared to control IL-18Rα-deficient mice. In contrast, anti-IL-18Rα and anti-IL-18Rβ antibody treatment tended to increase cisplatin nephrotoxicity in wild-type mice. Thus, signaling through IL-18Rα activates both inflammation-suppressing and pro-injury pathways in cisplatin-induced acute kidney injury.     

Successful treatment using tacrolimus plus corticosteroid in a patient with RA associated with MDS

We report a case of rheumatoid arthritis (RA) complicated by myelodysplastic syndrome (MDS) successfully treated by tacrolimus. A 57-year-old woman had persistent pain and swelling in bilateral wrist and knee joints, in addition to severe anemia and leukopenia. She was diagnosed with MDS and RA based on the results of bone marrow aspiration and the criteria of RA. Combination therapy with tacrolimus (1.5 mg day⁻¹) and prednisolone (10 mg day⁻¹) improved her bicytopenia and polyarthralgia.     

Serum level of interferon-gamma in autoimmune diseases.

Interferon-gamma is one of the cytokines which have various immunoregulatory functions. In the present study, the serum interferon-gamma level was determined in autoimmune diseases. It was increased in the active cases of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Since there was a positive correlation between the serum interferon-gamma level and the rate of peripheral mononuclear cells positive for HLA-DR antigen in systemic lupus erythematosus, circulating interferon-gamma might have a biological functions as suggested by many in vitro studies. In rheumatoid arthritis and Sj?gren's syndrome, there was no correlation between the serum interferon-gamma level and the clinical findings. These data suggest that interferon-gamma might be associated with the pathogenesis of autoimmune diseases such as SLE and MCTD, and it can be one of the indices for their disease activity.     

μ-Heavy Chain Disease Associated with Systemic Amyloidosis

μ-heavy chain disease (HCD) is very rare, with only 30 cases reported in the literature. We report a patient with μ-HCD associated with systemic amyloidosis. The diagnosis of μ-HCD was based on findings of μ-heavy chain fragments in the serum, Bence Jones proteinuria and vacuolated plasma cells in the bone marrow. To our knowledge, this is the third case in which systemic amyloidosis led to the patient's death.