Increased risk of osteoporotic vertebral fracture in rheumatoid arthritis patients with new-onset cardiovascular diseases: a retrospective nationwide cohort study in Taiwan.

INTRODUCTION: Both cardiovascular diseases (CVD) and osteoporosis are common comorbidities in rheumatoid arthritis (RA) patients. Although accumulating evidence indicates a link between CVD and osteoporotic fracture, whether CVD contributes to osteoporotic fracture risk in RA has yet to be explored. We examined the incidence rate and risk factors of osteoporotic vertebral fracture in RA patients with new-onset CVD (RA-CVD) and evaluated the effects of medications on such fracture risk. METHODS: A retrospective study was conducted using a nationwide database from 2000 to 2010: 1267 RA-CVD and 1267 non-CVD patients were enrolled from 30,507 patients with newly diagnosed RA. The main outcome was the development of osteoporotic vertebral fracture. After being adjusted for age, gender, and comorbidities, the Cox proportional hazard model was used to identify independent factors contributing to osteoporotic vertebral fracture. RESULTS: The adjusted hazard ratio (aHR) of developing osteoporotic vertebral fracture was 1.47-fold greater in RA-CVD group than in non-CVD group (95% confidence interval 1.19-1.81, p < 0.001). Both the age above 40 years and female gender were significant risk factors for developing osteoporotic vertebral fracture in RA-CVD patients. Using patients not taking medication as a reference group, the aHR of osteoporotic vertebral fracture was significantly lower in those receiving statins (0.50), low-dose corticosteroids (0.57), or hydroxychloroquine (0.12). CONCLUSIONS: The risk of osteoporotic vertebral fracture was significantly increased in RA-CVD patients, particularly women above 40 years of age, and could be reduced by statin therapy. However, the protective effect of low-dose corticosteroids or hydroxychloroquine on osteoporotic vertebral fracture risk needs further validation.

Increased risk of hepatitis B virus reactivation in systemic lupus erythematosus patients receiving immunosuppressants: a retrospective cohort study.

Objective We aimed to investigate risk of hepatitis B virus reactivation in systemic lupus erythematosus patients with different hepatitis B virus infection statuses receiving immunosuppressive therapy. Methods We retrospectively analyzed systemic lupus erythematosus patients with positive hepatitis B surface antigen or anti-hepatitis B core IgG antibody who underwent immunosuppressive therapies from January 2001 to December 2012 at a medical center in Taiwan for evidence of hepatitis B virus reactivation. Results During this period, 906 out of 3125 patients who were diagnosed with systemic lupus erythematosus received screening tests for hepatitis B virus. Thirty-eight patients were identified as hepatitis B surface antigen-positive. Fifteen of 38 (39.5%) hepatitis B surface antigen-positive patients developed hepatitis B virus reactivation, and 53.3% of these patients experienced severe hepatitis flare. Three of 157 hepatitis B surface antigen-negative/anti-hepatitis B core IgG antibody-positive patients (1.9%) experienced hepatitis B surface antigen seroreversion after immunosuppressive therapy. Five patients received prophylactic or preemptive antiviral therapy and none of them developed hepatitis B virus flares. A daily dose of prednisolone greater than 5 mg was a risk factor for hepatitis B reactivation by multivariate logistic analysis. Conclusions The risk of hepatitis B virus reactivation is high in lupus patients receiving immunosuppressive therapy. Antiviral prophylaxis or preemption can effectively reduce the incidence of hepatitis B virus reactivation in lupus patients.

Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics.

The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis.

T helper type 17 (Th17) cells, a novel distinct subset of Th cell, can secrete interleukin (IL)-17 in humans. Although recent data suggest that Th17 cells and IL-17 play an important role in the pathogenesis of lupus nephritis (LN), the expression of Th17-related cytokines in the kidneys of SLE patients has not been studied in detail. In the present study, we investigated circulating Th17-cell frequencies using flow cytometry and serum Th17-related cytokine levels by enzyme-linked immunosorbent assay (ELISA) in 24 LN patients (17 patients with class IV and seven patients with class V) and 12 healthy controls. We also investigated glomerular Th17-related cytokine expression in LN patients and minimal change nephropathy (MCN) patients using immunohistochemistry. Our results showed significantly higher median frequencies of circulating Th17 cells in LN patients (0.68%) than in healthy controls (0.12%, p < 0.001). Serum levels of IL-17, IL-6 and IL-23 were significantly higher in LN patients (median 7.26, 232.60 and 37.01 pg/ml, respectively) than in healthy controls (median 0.82, 34.60 and 7.42 pg/ml, respectively; all p < 0.001). Circulating Th17-cell frequencies were positively correlated with SLEDAI, renal SLEDAI and histological activity index, the degree of cellular crescent and endocapillary proliferation. Significantly higher levels of glomerular IL-17 and IL-23 expression were observed in renal biopsies from class IV LN patients as compared to those from MCN patients and normal controls. Glomerular IL-17 and IL-23 expression levels were positively correlated with renal SLEDAI and histological activity index for LN patients. Our results suggest the potential role of the IL-23/Th17 axis in the intra-renal inflammation of SLE.

RNA interference-mediated silencing of Foxo3 in antigen-presenting cells as a strategy for the enhancement of DNA vaccine potency.

The transcription factor Forkhead box O3 (Foxo3) has a critical role in suppressing the expansion of antigen-specific effector T-cell populations; hence, Foxo3 is a potential target for enhancing the antitumor immunity of cancer vaccines. In this report, we evaluated the potential of RNA interference (RNAi)-mediated silencing of Foxo3 in antigen-presenting cells as an adjuvant for HER2/neu DNA cancer vaccines. Bicistronic plasmids expressing the N-terminal extracellular domain of human HER-2/neu and the Foxo3 short hairpin RNA (hN'-neu-Foxo3 shRNA) or the scrambled control (hN'-neu-scramble shRNA) were subcutaneously injected into mice by gene gun administration to elicit antitumor immunity against p185neu-overexpressing MBT-2 bladder tumor cells. We found that mice treated with hN'-neu-Foxo3 shRNA showed greater reductions in tumor growth and longer survival times than mice treated with hN'-neu-scramble shRNA, indicating that the silencing of Foxo3 enhanced the antitumor efficacy of the HER-2/neu cancer vaccine. Cytotoxicity analyses further revealed that the Foxo3 shRNA-enhanced antitumor effect was associated with significant increases in the number of functional CD8(+) T cells and in the levels of cytotoxic T lymphocytes activity. Interleukin-6 was induced by hN'-neu-Foxo3 shRNA treatment but did not have a critical role in the antitumor effect of the hN'-neu-Foxo3 shRNA vaccine. Moreover, in vivo lymphocyte depletion analyses confirmed that the antitumor efficacy of the hN'-neu-Foxo3 shRNA vaccine depended on functional CD8(+) T cells. Finally, Foxo3 suppression was shown to markedly improve the effect of the HER-2/neu DNA vaccine in limiting the growth and lung metastases of MBT-2 cells. Overall, these results support RNAi-mediated silencing of Foxo3 as an effective strategy to enhance the therapeutic antitumor effect of HER-2/neu DNA vaccines against p185neu-positive tumors.

Antinucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis.

The objective of this study is to evaluate the correlation between antinucleosome antibodies and renal pathological activity in patients with proliferative lupus nephritis (LN). We evaluated 36 patients with proliferative LN, 14 non-renal lupus patients and 10 healthy volunteers. Lupus activity was assessed using the British Isles Lupus Assessment Group 2004 (BILAG 2004) index, serum anti-double stranded DNA (anti-dsDNA) levels, serum complement levels and daily urinary protein levels. All 36 lupus nephritis patients received renal biopsy. Antinucleosome antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Our results showed that levels of serum antinucleosome antibodies were significantly higher in LN patients (median 90.35 units/ml, interquartile range [IQR] 37.38-135.23) than in non-renal SLE patients (median 5.45 units/ml, IQR 2.6-28.93, p <0.05) and in healthy volunteers (median 3.35 units/ml, IQR 2.95-5.23, p <0.001). Serum levels of antinucleosome antibodies were positively correlated with BILAG index (Spearman's r = 0.645, p <0.001) and serum anti-dsDNA antibody levels (r(s) = 0.644, p <0.01), while serum levels of antinucleosome antibodies were negatively correlated with serum levels of C3 (r(s) = -0.400, p <0.01) and C4 (r(s) = -0.300, p <0.05). Serum levels of antinucleosome antibodies were positively correlated with the histological activity index of LN (r(s) = 0.368, p <0.05). However, there was no significant correlation between serum levels of antinucleosome antibodies and the histological chronicity index. In conclusion, the serum level of antinucleosome antibodies is a potential biomarker for early recognition of renal involvement and evaluation of disease activity in SLE. Our preliminary results suggested that serum levels of antinucleosome antibodies might be a potential biomarker in evaluating pathological activity of LN.

Use of a recombinant protein containing major epitopes of hnRNP G to detect anti-hnRNP G antibodies in dogs with systemic lupus erythematosus.

The objective of this study was to express major epitopes of heterogeneous nuclear ribonucleoprotein G (hnRNP G) for detecting anti-hnRNP G antibodies in dogs with systemic lupus erythematosus (SLE). HnRNP G cDNA clone was isolated from HEp-2 cells, and a DNA fragment encoding immunodominant region (residues 189-272) of hnRNP G (hnRNP Gi) was subcloned into pET32 vector to construct a prokaryotic expression plasmid named pEThnRNPGi. After induction, Escherichia coli carrying pEThnRNPGi expressed a recombinant protein of 28 kDa, comprising recombinant hnRNP Gi and fusion tag. Purified recombinant hnRNP Gi protein was further analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its identity was confirmed. Western blot analysis showed that recombinant hnRNP Gi was specifically recognized by anti-hnRNP G positive sera of SLE dogs, and not by negative control sera. In conclusion, recombinant hnRNP Gi protein expressed in this study may serve as a useful reagent to assist in the immunological diagnosis of canine SLE.

Gallium-67 scintigraphy to predict response to therapy in active lupus nephritis.

UNLABELLED: Gallium-67-citrate has been used to detect inflammation for decades, and 67Ga uptake usually indicates an active, potentially curable lesion. In this study, we determined the value of 67Ga renal scintigraphy for predicting response to therapy in patients with lupus nephritis. METHODS: Forty-seven patients with lupus nephritis and abnormal serum creatinine or elevated 24-hr urine protein were enrolled. Delayed 48-hr 67Ga imaging was performed to evaluate 67Ga uptake by the kidneys. Serum creatinine and 24-hr urine protein values were obtained at the beginning of this study and after 1 yr of treatment. Serum creatinine was considered abnormal at levels greater than or equal to 1.4 mg/dl and 24-hr urine protein at levels greater than or equal to 1.0 g/day. When the value of serum creatinine or 24-hr urine protein obtained 1 yr after treatment was in the normal range or was 50% of the initial abnormal value, the patient was considered to have good response to treatment. RESULTS: Gallium-67 renal scan showed good correlation with the response to therapy in patients with lupus nephritis. In the negative 67Ga scan group, no significant changes in laboratory data were noted between onset of this study and after 1 yr of therapy. In the positive 67Ga scan group, there were significant decreases in serum creatinine and 24-hr urine protein levels 1 yr after treatment, especially in 24-hr urine protein, with p values of 0.019 and 0.0007 respectively, by Student's t-test for dependent samples. Moreover, 11.5% of patients with a negative 67Ga scan had a good response to treatment, whereas 71.4% of patients with a positive 67Ga scan had a good response to treatment. CONCLUSION: We suggest that 67Ga renal scan is a valuable predictor of response to therapy in patients with lupus nephritis.

Technetium-99m-HMPAO brain SPECT in systemic lupus erythematosus with CNS involvement.

UNLABELLED: Functional brain SPECT is playing an increasingly important role in evaluating CNS conditions in patients with systemic lupus erythematosus (SLE). However, SPECT findings varied in different studies because of their small population. Furthermore, earlier researchers, being restricted by the resolution of the camera, might not have been able to evaluate deep-seated nuclei such as the basal ganglia and thalamus. In this study, we describe the different patterns of SPECT findings in SLE patients with CNS involvement. METHODS: Seventy-two SLE patients (aged 14-67 yr; mean 33.2 yr) were divided into three groups: Group 1 with definite neuro-psychiatric disorder (including stroke, seizures and psychosis); Group 2 with minor neuropsychiatric disorders (headache, dizziness and recent memory impairment); and Group 3 without any neuropsychiatric symptoms or signs. Ninety minutes after injection of 1110 MBq 99mTc-HMPAO, brain SPECT was performed using a dual-head camera and fan-beam collimator. In addition, MRI and an electroencephalography (EEG) were also performed. RESULTS: SPECT findings were normal in 87% of the Group 3 patients and abnormal in all Group 1 patients; 84.6% of the Group 2 patients had abnormal SPECT findings. The parietal, frontal and temporal lobes were the most common areas of CNS involvement. Parietal lobes were involved in 95.6% of Group 1 patients and 80.7% in Group 2 patients. Frontal lobes were involved in 56.5% of Group 1 patients and 65.3% of Group 2 patients. Temporal lobes were involved in 56.5% of Group 1 patients and 46.1% of Group 2 patients. The basal ganglion was involved in about 30% of Group 1 patients and 11.5% of Group 2 patients, while the thalamus and cerebellum were less involved in neuropsychiatric SLE. MR images showed less sensitivity in the detection of CNS involvement than the SPECT and were normal in 27.3% of patients with definite neuropsychiatric disorders. The EEG and anticardiolipin antibody did not correlate well to the clinical diagnosis. CONCLUSION: HMPAO brain SPECT had the best correlation with the clinical diagnosis and may provide additional and objective information on SLE patients with potential CNS involvement.

Technetium-99m-pyrophosphate scintigraphic findings of intestinal perforation in dermatomyositis.

Gastrointestinal complications are more common in children than in adults and present a serious problem with dermatomyositis. We report on a 66-yr-old man with dermatomyositis who suffered from intestinal perforation. The abdominal plain radiograph revealed only dilatation of the intestinal loops; increased radioactivity, however, was clearly demonstrated in the early 5-min and delayed 3-hr 99mTc-pyrophosphate images.

Technetium-99m-HMPAO SPECT and MRI of brain in patients with neuro-Behçet's syndrome.

UNLABELLED: Involvement of the brain is one of the most important complications of Behçet's disease (BS). It is difficult to diagnose, however, because of the lack of effective imaging methods. METHODS: Thirteen BS patients with neuropsychiatric symptoms or signs [Neuro-Behçet's syndrome (NBS)] were included in this study. We combined two routine brain imaging modalities-brain SPECT with 99mTc-hexamethyl propyleneamine oxime (HMPAO) and brain MRI-with clinical manifestations to diagnose brain involvement. RESULTS: Technetium-99m-HMPAO brain SPECT findings were abnormal in 100% (13/13) of patients. Brain MRI findings were abnormal in 31% (4/13) of patients. Gray matter was involved more commonly than white matter. In the gray matter, the cerebral cortex was the most commonly involved area and the cerebellum was the least commonly involved area in NBS. CONCLUSION: SPECT is a more sensitive and useful tool in detecting brain involvement in NBS patients compared with brain MRI. The combination of HMPAO and MRI is necessary to detect brain lesions in both gray and white matter in NBS.

Technetium-99m-HMPAO brain SPECT in Sjögren's syndrome.

UNLABELLED: Technetium-99m-hexamethylpropylene amine oxime (HMPAO) brain images with fanbeam SPECT, in combination with surface three-dimensional display, were used to detect basal ganglion and cerebral cortex anomalies in Sjögren's syndrome patients. METHODS: Forty-eight female Sjögren's syndrome patients with normal brain CT or magnetic resonance imaging findings were enrolled in this study and were investigated using 99mTc-HMPAO brain images with fanbeam SPECT and surface three-dimensional display. These patients were separated into two subgroups. Group 1 consisted of 38 patients with definite neuropsychiatric symptoms/signs and Group 2 consisted of 10 patients without any neuropsychiatric symptoms/signs. RESULTS: Fanbeam SPECT demonstrated unilateral or bilateral hypoactivity of basal ganglia and thalamus in 14% and 0% of patients in Groups 1 and 2, respectively. Using surface three-dimensional display of the brain, local hypoactivity anomalies were found in the brain cortex of 53% and 20% of patients in Groups 1 and 2, respectively. In Group 1 patients, parietal lobes were the most common areas of brain involvement. The cerebellum and thalamus were the least common areas of brain involvement. In Group 2 patients, parietal and temporal lobes were the most common areas of brain involvement. CONCLUSION: This study suggests that 99mTc-HMPAO brain imaging with fanbeam SPECT, in combination with surface three-dimensional display, is a sensitive tool for detecting regional cerebral anomalies in Sjögren's syndrome patients with and without neuropsychiatric symptoms/signs.

Regional cerebral blood flow and glucose metabolism in Sjögren's syndrome.

UNLABELLED: Involvement of the brain is one of the most important complications of Sjögren's syndrome (SS). However, diagnosis of brain involvement in SS patients is difficult due to the lack of effective imaging methods. In this study, we compared two updated brain imaging modalities, 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET and 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT, in SS patients with neuropsychiatric manifestations, to detect glucose metabolism of the brain and regional cerebral blood flow. METHODS: Sixteen primary female SS patients with normal brain MRI findings were enrolled in this study. RESULTS: Technetium-99m-HMPAO SPECT findings were abnormal in 13 (81%) patients. Parietal and temporal lobes were the most common areas of brain involvement. Fluorine-18-FDG PET findings were abnormal in 3 (19%) patients. Temporal lobes were the most common areas of brain involvement. CONCLUSION: We conclude that brain HMPAO SPECT has better correlation with clinical manifestations than brain FDG PET or CT/MRI.

Evaluation of regional cerebral blood flow with 99mTc-HMPAO in primary antiphospholipid antibody syndrome.

UNLABELLED: In this study, 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT was used to evaluate the regional cerebral blood flow (rCBF) of the brain in patients with primary antiphospholipid antibody syndrome (PAPS). METHODS: Twenty-two women who were PAPS patients, aged 28-60 y, with mild neuropsychiatric manifestations and normal brain MRI findings were enrolled in this study. Brain HMPAO SPECT was performed to detect brain abnormalities. Meanwhile, serum anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) were measured. RESULTS: HMPAO SPECT revealed hypoperfusion lesions in 16 of 22 (73%) PAPS patients. Cerebral cortex and cerebellum were the most and the least commonly involved areas, respectively. Eighteen of 22 (82%) and 14 of 22 (64%) patients had positive ACA and positive LA, respectively. ACA and LA results were related to HMPAO SPECT findings. CONCLUSION: HMPAO SPECT is a sensitive tool for detecting brain abnormalities in PAPS patients with only mild neuropsychiatric manifestations and normal brain MRI findings.

Gangliosides suppression of murine lymphoproliferation and interleukin 1 production.

Studies were carried out to determine whether inhibition of gangliosides on lymphoproliferation was related to interleukin (IL)-1. The results showed that gangliosides, GM1 and GT1b were able to inhibit the proliferation of spleen lymphocytes from C57BL/6J mice in dose-dependent fashion, whereas asialo-GM1 was not inhibitory. However, gangliosides, GM1 and asialo-GM1 did not suppress the production of IL-1 in Salmonella typhosa lipopolysaccharide (LPS)-induced peritoneal adherent cells. Various types of LPS including S. enteritidis, S. minnesota and Escherichia coli 055:B5 were used to stimulate the production of IL-1 in adherent cell cultures. The IL-1 production was not affected by gangliosides, GD1a and GD1b. Although GT1b suppressed IL-1 production of human monocytes to 82% of control level it did not, however, affect the IL-1 production of murine adherent cells. Thus, the inhibitory mechanism of gangliosides on murine immune cells remains unclear, and warrants further study.

Collagen induces cytokine production by synovial fluid mononuclear cells in rheumatoid arthritis.

Synovial fluid (SF) mononuclear cells (MNC) from 13 patients with rheumatoid arthritis (RA) and 12 patients with other arthritic diseases (OD) including osteoarthritis (OA), gout and spondyloarthritis (SA) were cultured in the presence of collagen types I and II or lipopolysaccharide (LPS) for 24 h. Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the SF and culture supernatants were assayed using ELISA. The results showed that one-half of the RA patients with high SF monocyte count had high SF IL-6 levels that coincided with the high spontaneous release of IL-6 by SF MNC. In the other RA patients with lower SF monocyte count, type II collagen induced significantly higher IL-1 beta than the medium control levels by SF MNC (P < 0.01) or that of the other diseases (P < 0.01). Similarly, type II collagen-induced IL-6 and TNF-alpha production rose significantly (P < 0.01) from SF MNC of RA but less from OD (P < 0.05). In addition, type I collagen could also induce IL-1, IL-6 and TNF-alpha in these samples from RA and OD patients but was less potent than type II collagen. Our results indicate that collagen-induced cytokines may be important in the pathogenesis of the disease.

Prevalence of subclinical cryoglobulinemia in maintenance hemodialysis patients and kidney transplant recipients.

We studied the prevalence and the clinical spectrum of cryoglobulinemia (Cryo) among 101 maintenance hemodialysis (HD) patients and 148 kidney transplant (KT) recipients, with or without chronic hepatitis C virus (HCV) infection. Cryo was present in 32% (16 of 50) of the HCV-positive HD patients, 5.9% (3 of 51) of the HCV-negative HD patients, 37.8% (28 of 74) of the HCV-positive KT recipients, and 27% (20 of 74) of the HCV-negative KT recipients. Cryoprecipitate in 56.3% (9 of 16) of the HCV-positive Cryo HD patients and 53.8% (14 of 26) of the HCV-positive Cryo KT recipients contained HCV-RNA. Interestingly, the cryocrit values among HD and KT patients were much lower than these in other reports on nonrenal failure cases. Also, the cryoglobulinemic syndrome (with purpura, arthralgia, etc.) in HD and KT patients with Cryo were not common (Tables 1 and 2). There was not correlation between Cryo and age,sex, and liver function. Only longer duration of end-stage renal disease was noted in these patients. In addition, we suggested that KT patients are more susceptible to having Cryo. Further studies are necessary to better define whether any other subclinical viral or nonviral chronic infection may induce Cryo in HCV-negative KT recipients.

Kikuchi disease in systemic lupus erythematosus: clinical features and literature review.

Kikuchi disease (histiocytic necrotizing lymphadenitis) is a rare, benign entity which predominantly affects young women. The disease usually presents with painful or painless enlarged cervical lymph nodes accompanied with fever. The cause of the disease is uncertain and only 17 cases in the literature have been reported in the past to be associated with systemic lupus erythematosus (SLE). We report four cases of SLE with Kikuchi disease in Taiwan. This is the first report regarding Kikuchi disease and SLE in Taiwan. All patients are female. The mean age is 30 (ranging from 21 to 35 years). The mean history of SLE is 4 years (ranging from 10 days to 8 years). Three of our patients (75%) developed Kikuchi disease accompanied with flare-up of lupus activity, and the other one had Kikuchi disease simultaneously with the onset of SLE. One patient had ribosomal-P antibodies, one had ribonuclear protein (RNP) antibodies and none had antibodies to Ro(SSA) or La (SSB). The cause of association of Kikuchi disease with SLE is still unknown. From our cases, the high frequency of flare-up of lupus disease activity accompanied with the onset of Kikuchi disease and the simultaneous occurrence of these two diseases indicate that they are not independent events. We speculate that Kikuchi disease may be one of the manifestation of SLE.

Glomerulonephritis in ankylosing spondylitis.

There have been a few reports suggesting the association between glomerulonephritis (GN) and ankylosing spondylitis (AS). The reported glomerulonephritides include IgA nephropathy, mesangial proliferative GN and membranous nephropathy. From January 1983, through December 1984, we observed 5 cases of GN among 116 cases of definite AS. Three of them were IgA nephropathy. The other two were mesangial proliferative GN, with IgM deposit in one case and isolated C3 deposit in another. Microscopic hematuria was observed in all of them. The renal function and 24-hour urine protein excretion were all within normal limits. Serum IgA level increased in all but the case of mesangial proliferative GN with IgM deposit. All except one had the antigen of HLA-B27. Serum IgA level was determined in 78 cases (86 estimations) of AS. The mean value was 399.6 +/- 15.0 mg/dl (mean +/- SE) (normal range: 100-350 mg/dl). Fifty-four of them (63%) had a value higher than 350 mg/dl. The interrelationship of AS and IgA nephropathy was discussed.