Successful tocilizumab and tacrolimus treatment in a patient with rheumatoid arthritis complicated by systemic lupus erythematosus.

We report a 37-year-old female of intractable rheumatoid arthritis (RA) complicated by systemic lupus erythematosus (SLE), who was successfully treated with a combination of tocilizumab (TCZ) and tacrolimus. She was diagnosed with RA when she was 21 years old, and was administered oral prednisolone, injectable gold and salazosulfapyridine, but deformity of her hands gradually developed. She developed high fever and thrombocytopenia when she was 35 years old. Renal involvement, pericarditis, positive antinuclear antibody and high level of anti-double-stranded DNA antibody were found and the patient was diagnosed with SLE. Polyarthritis and immunological abnormalities developed despite aggressive immunosuppressive therapy including high-dose corticosteroids and intravenously administered cyclophosphamide. Tacrolimus (TAC) therapy gave only partial improvement of joint symptoms. After the initiation of combination therapy with TCZ, not only was a complete remission of RA obtained, but also the serum levels of SLE markers dramatically decreased. Our report suggests the possibility that this combination therapy is effective in treating SLE as well as RA.

Evaluation of average amount of cerebral blood flow measured by brain perfusion index in patients with neuropsychiatric systemic lupus erythematosus.

We used the brain perfusion index (BPI), an indicator of the average amount of cerebral blood flow (CBF), to evaluate the usefulness of the average amount of CBF for neuropsychiatric systemic lupus erythematosus (NPSLE). Of the seventy three SLE patients examined in this study (total 100 scans), 16 patients (23 scans) had already been diagnosed with NPSLE based on clinical symptoms indicative of central nervous system involvement. In addition, 12 patients (17 scans) exhibited the antiphospholipid antibody syndrome (APS). BPI is significantly influenced by age and we therefore used the BPI ratio (ratio of age predicted BPI to measured BPI value) for each assessment. The mean BPI value of 100 scans was 11.2 +/- 2.79, and the mean BPI ratio was 0.99 +/- 0.24 in all SLE patients. The mean BPI ratio among NPSLE (0.84 +/- 0.19) was significantly lower than that of the non-NPSLE patients (1.04 +/- 0.24) (P < 0.0005). However, there was no difference in the mean BPI ratio between APS patients (0.98 +/- 0.24) and non-APS patients (0.99 +/- 0.25). These results indicate that the mean CBF assessed by the BPI ratio using SPECT is of use in the evaluation of central nervous system involvement in SLE patients.

[Brain lesion in congenital myotonic dystrophy].

Congenital myotonic dystrophy (CMyD) affects the brain, causing mental changes and psychomotor retardation. However, the pathophysiology of the brain dysfunctions in CMyD remain to be clarified. We described two cases of CMyD with brain abnormalities. Case 1 was diagnosed as having ventricular dilation at 17 days after birth, and died at 3 years and 6 months. Case 2 was diagnosed as having ventricular dilation at birth, and died at 1 year and 3 months. Pathologically, both cases showed remote hypoxic ischemic brain damage and leptomeningeal glioneuronal heterotopia (LGH). In our patients, the white matter changes may have been caused by perinatal asphyxia, and LGH by embryological abnormalities. Taken our data and those of previous reports together, it is suggested that cerebral abnormalities in CMyD are ascribed to both hypoxic ischemic changes and histogenetic abnormalities.

Cloning and analysis of HLA class I cDNA encoding a new HLA-C specificity Cx52.

HLA-C loci frequently have an unclassifiable "blank (CwBL)" specificity. It is unclear whether HLA-C specificities associated with the haplotypes of A24 Bw52 CwBL DR2 DQw1 and Aw33 B44 CwBL DRw13 DQw1 in Japanese (tentatively named Cx52 and Cx44, respectively) really exist. Southern hybridization experiments revealed that restriction enzyme-cleaved genomic DNA from AKIBA, consanguineous HLA homozygote, two other homozygotes with the former haplotype, and three homozygous cells with the latter haplotype hybridized strongly with an HLA-C-specific probe. We have screened the cDNA library constructed from AKIBA to isolate cDNA clones encoding the putative Cx52 antigen, and picked up 103 cDNA clones with HLA-class I DNA probes as possible candidates. By restriction enzyme mapping and Southern hybridization of selected clones, we identified three isotypes of cDNA clones, pA01, pB55, and pC68, which appeared to encode A24, Bw52, and Cx52, respectively. The nucleotide sequence of pC68 showed higher homology with exons of the HLA-C gene than with those of the HLA-A and HLA-B genes, especially in exons 6-8 which include the HLA-C-specific region. Comparison of amino acid sequences showed more than 86% homology among Cw1, Cw2, Cw3, and new pC68-encoded Cx52 proteins. These results support the notion that the inability to define C antigens serologically in this Cx52 haplotype is not due to a HLA-C gene deletion or mutation, but to the absence of typing sera.