Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan.

We studied the clinico-pathological differences among PR3-ANCA-positive granulomatosis with polyangiitis (PR3-GPA), MPO-ANCA-positive GPA (MPO-GPA) and microscopic polyangiitis (MPA). ANCA-associated vasculitis (AAV) was classified using the European Medicines Agency classification. We retrospectively analyzed 38 patients with GPA and 41 with MPA treated in eight hospitals in Japan. Of the patients with GPA, 17 were positive for MPO-ANCA, and 15 for PR3-ANCA. All patients with MPA were MPO-ANCA positive. The mean ages of those with MPO-GPA were 69.6 years old, 10 years older than those with PR3-GPA. The majority (82 %) of patients with MPO-GPA were woman, a significantly greater proportion than for PR3-GPA. We also found that ear, nose and throat (ENT), nervous system involvement were significantly more common in MPO-GPA, but renal function was less impaired than those with MPA. Both PR3-GPA and MPO-GPA relapsed more frequently than MPA, but overall survival was significantly better (P < 0.01 and P < 0.05, respectively). Univariate analysis identified the following factors as predictors of a poor prognosis: MPA (P < 0.01), pulmonary UIP pattern (P < 0.005) Cr ≥ 1.7 mg/dl (P < 0.01) and absence of ENT involvement (P < 0.05), which were characteristics of MPA. In our cohort, MPO-GPA was most likely to affect older women and was associated with otitis media, nervous system involvement, mild renal impairment and more favorable outcome. It is clinically useful to differentiate MPO-GPA from MPA and PR3-GPA in patients with AAV.

Lymphoplasmacytic lymphoma with IgG-κ paraproteinemia presenting as a hepatic bulky mass.

Lymphoplasmacytic lymphoma (LPL) usually involves bone marrow (BM) and sometimes lymph nodes and spleen. LPL presenting as a hepatic mass lesion is extremely rare, with only one case reported in the English literature. A 70-year-old Japanese female presented to us with a right hypochondriac mass with tenderness. Computed tomography (CT) revealed a 14 cm-sized bulky hepatic mass. Laboratory findings showed a normal white blood cell count of 4.1×109/L with 4% plasmacytoid lymphocytes; normocytic anemia, Hb 9.4 g/dL; high soluble IL-2 receptor level, 2,290 U/mL; and elevated IgG, 10,306 mg/dL. Furthermore, IgG-κ monoclonal protein was detected. 18F-fluorodeoxyglucose-positron emission tomography/CT revealed abnormal uptake in the liver mass; left supraclavicular, parasternal, abdominal, and left inguinal lymph nodes; and bilateral lung bases. Magnetic resonance imaging showed no bone lesions. BM aspiration and liver biopsy showed predominant infiltration of small lymphocytes admixed with plasmacytoid lymphocytes and plasma cells. In the liver specimen, lymphoepithelial lesions were not observed. The small lymphocytes were positive for CD20, CD79a, and bcl-2, and negative for CD5, CD10, cyclin D1, and IRTA1; plasma cells in BM were positive for CD19, CD45, IgG, and κ-chain, and negative for CD20, and CD56. MYD88 L265P mutation, reported in approximately 40% of non-IgM LPL cases, was not detected in the liver specimen and BM cells. The frequency is lower than that of typical IgM LPL. These findings led us to a diagnosis of LPL with IgG-κ paraproteinemia. The patient underwent four courses of R-CHOP and two courses of Bendamustine-R. Partial remission was achieved.

Association of killer cell immunoglobulin-like receptor 2DL5 with systemic lupus erythematosus and accompanying infections.

OBJECTIVE: Identification of the association of killer cell immunoglobulin-like receptor (KIR) genes with SLE and accompanying infections. METHODS: Presence or absence of all 14 KIR genes was studied for association with SLE by case-control studies. A total of 417 SLE cases, 72 RA cases and 256 controls, all of Japanese descent, were enrolled. RESULTS: The carrier frequency of KIR2DL5 was significantly decreased in SLE patients compared with healthy controls [39.3 vs 50.4%; odds ratio (OR) = 0.64; 95% CI 0.36, 0.92; P = 0.005). When the prevalence of severe infections was analysed in 184 SLE patients, whose medical records were available, KIR2DL5 carriers were at an increased risk of overall infection and viral infection (crude OR = 2.66; 95% CI 1.43, 4.92; P = 0.017 and crude OR = 2.31; 95% CI 1.15, 4.62; P = 0.017, respectively). After adjusting for methylprednisolone pulse and/or cyclophosphamide pulse therapy, KIR2DL5 carriers were at significantly greater risk of infectious events overall (adjusted OR = 2.45; 95% CI 1.24, 4.81; P = 0.0095). However, KIR2DL5 carriers were marginally associated with an increased risk of viral infectious events (adjusted OR = 2.03; 95% CI 0.94, 4.41; P = 0.0718). CONCLUSION: KIR2DL5 was significantly associated with a decreased risk of SLE as well as an increased risk of infectious events overall in SLE patients. Our data suggest a further role of KIRs in the pathogenesis of autoimmune diseases and infection.

Systemic vasculitis associated with alphal-antitrypsin deficiency.

We describe a rare case of systemic vasculitis associated with alpha1-antitrypsin (alpha1-AT) deficiency. Mutational analysis of the alpha1-AT gene in this patient revealed a homozygous alpha1-AT Mnichinan variant. Alpha1-AT possesses broad-spectrum inhibitory activity against many serine proteases, including human neutrophil elastase, to help maintaining the crucial balance between proteases and protease inhibitors. The increase in free protease activity in the context of alpha1-AT deficiency may induce exacerbation of the vasculitis. This serious genetic defect severely affects the balance between a protease and a protease inhibitor at the pathological site.

[Microbiological and clinical studies of Haemophilus influenzae isolated at Kitakyushu Municipal Medical Center from 1996 through 1999].

Epidemiological and microbiological studies were carried out using 575 strains of Haemophilus influenzae isolated from clinical specimens at Kitakyushu municipal medical center from January 1996 through December 1999. The strains isolated multiply were excluded. The strains of H. influenzae did not increase for 4 years, and were detected more in summer season, peaked in July, and less in winter season. Like the cases of Streptococcus pneumoniae, most (91.8%) of the strains was detected in the specimens from the respiratory tract, and also they were isolated mainly from infants under 4-years old (25.6%) and adults over 65-years old (24.2%) MICs of 7 antimicrobial agents, such as ampicillin (ABPC), sulbactam/ABPC, cefaclor, imipenem, panipenem, meropenem (MEPM), and levofloxacin (LVFX) were determined using broth microdilution methods. Among 575 strains of H. influenzae isolated from clinical specimens, 51 ABPC-resistant strains (8.9%) produced beta-lactamase, and 67 strains (11.6%) were beta-lactamase negative ampicillin resistant H. influenzae. The ABPC-resistant strains existed in 20.5%. Both of MEPM and LVFX showed excellent antimicrobial activity against H. influenzae including ABPC-resistant strains. Four cases of meningitis were reviewed. All of H. influenzae isolated possessed type b capsular antigen. All patients recovered by appropriate antimicrobial treatment. But one adult patient developed serious sequela.

A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case-control study and a meta-analysis.

OBJECTIVES: To perform a case-control study of a functional M196R polymorphism of tumour necrosis factor receptor type 2 (TNF-RII) in a Japanese population and a meta-analysis of all published reports on the polymorphism to investigate the association of the M196R polymorphism of TNF-RII with systemic lupus erythematosus (SLE). METHODS: The functional M196R polymorphism of TNF-RII was genotyped by using polymerase chain reaction combined with the subsequent single-strand conformation polymorphism (PCR-SSCP) analysis for screening, followed by nucleotide sequencing for confirmation. A total of 331 patients and 359 controls were subjected to a case-control study. A meta-analysis of the available case-control studies including all published data as well as our own data was performed to investigate the association of the functional M196R polymorphism of TNF-RII with SLE. RESULTS: Our case-control study did not show any significant association of a functional M196R polymorphism of TNF-RII with SLE, although there was a trend towards association. A meta-analysis of seven case-control studies in eight different ethnic populations including our own showed that 196M/R and 196R/R genotypes combined was significantly associated with an increased risk of SLE (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.04 to 1.60; p = 0.02). Stratification by ethnicity showed a more significant association in Asians, including Japanese, Korean and Vietnamese (OR 1.40, 95% CI 1.10 to 1.78; p = 0.006). The effect of the 196R allele on SLE was not clear in Caucasians. CONCLUSIONS: The 196R allele of the functional M196R polymorphism of TNF-RII is a risk factor for SLE, especially in the Asian population.