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ID PMID Title PublicationDate abstract
19194953 Automated microfluidic assay system for autoantibodies found in autoimmune diseases using 2008 Nov Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and autoimmune diabetes are characterized by the production of autoantibodies that serve as useful diagnostic markers, surrogate markers, and prognostic factors. We devised an in vitro system to detect these clinically pivotal autoantibodies using a photoimmobilized autoantigen microarray. Photoimmobilization was useful for preparing the autoantigen microarray, where autoantigens are covalently immobilized on a plate, because it does not require specific functional groups of the autoantigens and any organic material can be immobilized by a radical reaction induced by photoirradiation. Here, we prepared the microarray using a very convenient method. Aqueous solutions of each autoantigen were mixed with a polymer of poly(ethylene glycol) methacrylate and a photoreactive crosslinker, and the mixtures were microspotted on a plate and dried in air. Finally, the plate was irradiated with an ultraviolet lamp to obtain immobilization. In the assay, patient serum was added to the microarray plate. Antigen-specific IgG adsorbed on the microspotted autoantigen was detected by peroxidase-conjugated anti-IgG antibody. The chemical luminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All autoantigens were immobilized stably by this method and used to screen antigen-specific IgG. In addition, the plate was covered with a polydimethylsiloxane sheet containing microchannels and automated measurement was carried out.
19161416 The roles of IL-17A in inflammatory immune responses and host defense against pathogens. 2008 Dec T-helper 17 (Th17) cells are a newly discovered CD4(+) helper T-cell subset that produces interleukin-17A (IL-17A) and IL-17F. IL-17A plays important roles in allergic responses such as delayed-type hypersensitivity, contact hypersensitivity, and allergic airway inflammation. IL-17A promotes inflammation by inducing various proinflammatory cytokines and chemokines, recruiting neutrophils, enhancing antibody production, and activating T cells. IL-17A expression is also augmented in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Using mouse models of these diseases, we found that IL-17A plays a central role in their development. IL-6 is required for the development of Th17 cells and tumor necrosis factor functions downstream of IL-17A during the effector phase. IL-1 is important both for developing Th17 cells and eliciting inflammation. Th17 cells, like Th1 and Th2 cells, are involved in host defense against infections, but the contribution of these Th subsets to defense mechanisms differs among pathogens. The roles of IL-17F remain largely unknown. In this review, we introduce how IL-17A/IL-17F are involved in inflammatory immune responses and host defense mechanisms and discuss their relationship with other cytokines in the development of inflammatory and infectious diseases.
19089533 Clinical and histopathological features of myopathies in Japanese patients with anti-SRP a 2009 To elucidate the clinical and histopathological features associated with autoantibodies to the signal recognition particle (SRP), we have studied 23 Japanese patients with this specificity among 3,500 patients with polymyositis/dermatomyositis and other connective tissue diseases. Anti-SRP antibodies were determined based on analysis of RNA and protein components by immunoprecipitation assays. The pathological analysis was performed by using special stainings including alkaline phosphatase, myosin ATPase, and modified Gomori trichrome stainings. Twenty-one (92%) of these 23 patients had myositis, 8 of whom (38%) required cytotoxic agents or intravenous immunoglobulin therapy in addition to corticosteroid therapy. Four patients (16%) had rheumatoid arthritis, two of whom had no features of myositis. Muscle biopsy specimens of 11 patients were examined histologically in detail. All 11 had muscle fiber necrosis and/or regeneration, but only one had infiltration of inflammatory cells. Six of the 11 (55%) patients showed type I fiber predominance by ATPase staining, while eight control myositis patients without anti-SRP antibodies did not. There was no correlation of other neurogenic features in histology with the presence of anti-SRP antibodies. These studies suggest that anti-SRP autoantibodies are most likely to be related to myopathies that are resistant to corticosteroid therapy and without inflammation histopathologically.
18791967 [Diagnostics of autoimmune diseases]. 2008 Sep Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of special and rare autoantibodies that otherwise often remain undetected. Standardisation of autoimmune diagnostics is still underway and requires joint efforts by laboratories, clinicians and industry.
18783749 Prevention of musculoskeletal conditions in the developing world. 2008 Aug Musculoskeletal conditions are an increasingly common problem across the globe due to increased longevity and increased exposure to risk factors such as obesity and lack of physical activity. The increase is predicted to be greatest in developing countries, and there is thus an urgent need for the implementation of strategies and policies that will prevent and control these conditions. The ideal is modification of the risk factors in the whole community, and this will have wide-ranging health benefits as these risk factors are common to other major conditions. Changing people's behaviour is a challenge; targeting those at highest risk is potentially more effective, providing that there are both affordable ways of identifying those at risk and affordable interventions. Early intervention in those with a condition such as rheumatoid arthritis is probably the most cost-effective approach, but requires diagnostic capacity--in clinical skills and/or technology--as well as access to care. There is now much evidence for what can be achieved, but the challenge is how to implement these different strategies in developing countries where there are competing priorities for limited resources. The key strategy is to raise awareness among the public, health professionals, and policy makers of the importance of musculoskeletal health, of what can be achieved by prevention and treatment, and to ensure that policies reflect this. It is also necessary to educate the public to know when to seek care, and health-care workers to recognize the early signs of musculoskeletal conditions.
17596907 [Large granular lymphocyte leukemia]. 2007 Nov Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent. NK-LGL leukemias can be more aggressive. LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis. The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies. Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process. Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia. Long-lasting remission can be obtained with immunosuppressive treatments such as methotrexate, cyclophosphamide, and cyclosporine A. NK-LGL leukemias may be more aggressive and refractory to conventional therapy.
17521896 Patient-perceived benefit during one year of treatment with Doloteffin. 2007 Jun We recruited 114 patients (56 with chronic nonspecific low back pain, 37 with osteoarthritic knee and 21 with osteoarthritic hip pain) into a surveillance of the effects of taking Doloteffin at a dose providing 60 mg harpagoside per day for up to 54 weeks. Their symptoms and well-being were monitored at 4-6 week intervals by disease-specific and generic outcome measures, and the patients also kept a diary of their pain and requirement for rescue medication. The principal analyses were on the basis of Intention to Treat (ITT) with Last Value Carried Forward (LOCF). A Multivariate Analysis of Variance (MANOVA) indicated an appreciable overall improvement during the surveillance, similar in the Back, Knee and Hip groups. In separate ANOVAs, most of the individual outcome scores decreased significantly over time. Multiple regression analyses indicated that changes from baseline were independent of patients' characteristics. Additional analgesic requirements (which were very modest) declined during the year of surveillance. "Response during treatment", assessed according to criteria adapted from joint proposals of the Outcome Measures in Rheumatoid Arthritis Clinical Trials group and the Osteoarthritis Research Society International group, was achieved in 75% of patients, and was reflected in the percentages who rated the treatment as "good" or "very good". Adverse events were few and none were serious.
17511262 [The mechanism of TRACP 5b maturation]. 2007 Apr Serum tartrate resistant acid phosphatase 5b (TRACP 5b) is an isozyme of osteoclast origin. Indeed, measurement of TRACP 5b activity is used as an index of osteoclast activity. However, the precise mechanism of TRACP 5b maturation is unclear. This study aimed to clarify the mechanism of generation of TRACP 5b. We used a highly sensitive fiber-type DNA chip to investigate the mechanism of generation of TRACP 5b at the genetic level. Genes derived from three related cell types (monocytes, macrophages and osteoclasts) were compared. In addition, at the protein level, posttranscriptional modification was tested by Western blotting using an antiserum specific for the flexible loop region of TRACP 5. Our DNA chip study shows that genes implicated in oligosaccharide construction do not show significant differences in expression levels between the cell types under investigation. Strongly expressed Cathepsin K was observed in osteoclasts. Western blotting demonstrated that TRACP undergoes unique partial degradation during bone resorption, such that serum TRACP 5b lacks the flexible loop found in TRACP 5a. In conclusion, TRACP 5b generated by a specific posttranscriptional modification pathway undergoes partial digestion in resorption lacunae or inside osteoclasts. Serum TRACP 5b lacking the flexible loop differs from TRACP 5a in terms of optimum pH, isoelectric point, sugar chain and antigenicity. The measurement of TRACP 5b could therefore be of great use for monitoring of osteoporosis, rheumatoid arthritis and bone metastasis.
17498061 The mast cell IgG receptors and their roles in tissue inflammation. 2007 Jun Mast cells are effector cells of the innate immune system, but because they express Fc receptors (FcRs), they can be engaged in adaptive immunity by antibodies. Mast cell FcRs include immunoglobulin E (IgE) and IgG receptors and, among these, activating and inhibitory receptors. The engagement of mast cell IgG receptors by immune complexes may or may not trigger cell activation, depending on the type of mast cell. The coengagement of IgG and IgE receptors results in inhibition of mast cell activation. The Src homology-2 domain-containing inositol 5-phosphatase-1 is a major effector of negative regulation. Biological responses of mast cells depend on the balance between positive and negative signals that are generated in FcR complexes. The contribution of human mast cell IgG receptors in allergies remains to be clarified. Increasing evidence indicates that mast cells play critical roles in IgG-dependent tissue-specific autoimmune diseases. Convincing evidence was obtained in murine models of multiple sclerosis, rheumatoid arthritis, bullous pemphigoid, and glomerulonephritis. In these models, the intensity of lesions depended on the relative engagement of activating and inhibitory IgG receptors. In vitro models of mature tissue-specific murine mast cells are needed to investigate the roles of mast cells in these diseases. One such model unraveled unique differentiation/maturation-dependent biological responses of serosal-type mast cells.
17433868 B cells and the BAFF/APRIL axis: fast-forward on autoimmunity and signaling. 2007 Jun B-cell activation factor from the tumor necrosis factor family (BAFF) is a key survival factor during B-cell maturation -- a delicate immune checkpoint for B cells. Excessive BAFF production at this stage corrupts B-cell tolerance and leads to autoimmunity. Elevated serum BAFF levels have been detected in some patients suffering from various autoimmune conditions. The positive outcomes of currently ongoing clinical trials using BAFF-neutralising agents confirm that this factor plays a major pathological role in rheumatoid arthritis and in systemic lupus erythematosus. Almost a decade after its discovery, BAFF continues to occupy the main stage in Immunology, with more than one hundred BAFF-related articles published per year. In recent years, our understanding of cell signaling and autoimmune mechanisms in this system have seen major advances, refining new possibilities for therapeutic intervention.
17243191 Dissimilar aggregation processes govern precipitation and gelation of human IgM cryoglobul 2007 Mar Cryoglobulinemia is associated with a range of diseases including rheumatoid arthritis, B-cell malignancies, and chronic viral infections. This "cold-sensitivity" condition is caused by cryoglobulins that precipitate, gel, or occasionally crystallize in the cold. Clinical manifestations vary widely in severity, depending on many factors, including the type of cryoglobulin (monoclonal or mixed immunoglobulins) and the physical nature of the aggregates (precipitate, gel, or crystal). Dynamic light scattering (DLS) was used to examine the cold-induced precipitation or gelation of two human cryoglobulins, namely, Pot IgM and Yvo IgM. The DLS assay was highly reproducible, sensitive, and had low intra-assay variations for both IgM cryoglobulins. Distinct processes were revealed to contribute to precipitation and gelation of cryoglobulins. The precipitation of Pot IgM displayed a rapid transition from solution to solid phases, with a wide distribution of aggregate sizes. In contrast, the gelation of Yvo IgM progressed gradually across a broad temperature range to produce a relatively uniform gel matrix. Initial cryoglobulin concentrations determined the kinetics and critical temperatures for both precipitation and gelation. Moreover, the Yvo IgM was observed to have a distinct relationship between concentrations and mean hydrodynamic diameters or particle sizes. Concentration-dependent effects on particle sizes were present, but not as pronounced for the Pot IgM. Precipitation and gelation of cryoglobulins were also found to be differentially responsive to changes in the aqueous environment. Our results indicate that DLS is a rapid, reliable, and sensitive method for characterizing the nature of disease-associated cryoglobulins.
21794562 [Soft-tissue infections]. 2008 Oct One of the soft-tissue infections with a large clinical relevance is necrotizing fascitis produced by Streptococcus pyogenes and skin infections produced by Staphylococcus aureus, particularly due to the evermore frequent methylcillin (MRSA) resistant varieties. In necrotizing fascitis the diagnostic delay as well as the delay in the indication for surgical debridement influence both the prognosis and a high mortality related to these infections. Two clinical forms have been described: Type I caused by at least one anaerobic species in combination with facultative anaerobes, more frequent in diabetics or patients with peripheral vascular disease; type II, monomicrobial, produced by group A beta hemolytic Streptococcus and with a lesser frequency by Staphylococcus aureus. Among the recognized risk factors diabetes mellitus, peripheral vascular disease, chronic renal failure, alcoholism, cancer, malnutrition, steroid and/or immunosuppressant treatment and the use of intravenous parenteral drugs are widely recognized. Therapeutics is based on hemodynamic support, antibiotic therapy and an early surgical approach with the elimination of all of the necrotic and devitalized tissue. Infections frequently associated to community-acquired MRSA are those present in skin and soft-tissue. Some population groups have been described as at-risk, but there is also an increase in the number of patients with no risk factors. Also, national and international registries of anti-TNF therapies have demonstrated the increase of soft-tissue infections in patients with rheumatoid arthritis treated with these agents. Other biologic drugs such as rituximab, abatacept or anakinra do not seem to be associated to an increase in these infections.
18762934 Limits of add-on trials: antirheumatic drugs. 2009 Jan PURPOSE: This paper assesses the design of clinical studies used in the process of regulatory approval, focusing on how add-on studies affect regulatory decisions. METHODS: The sample case taken is that of the new agents for rheumatoid arthritis (RA) authorised by the European Medicine Agency (EMEA). The European Public Assessment Reports (EPARs) accompanying the marketing authorisations were the source of information on the studies presented in the registration dossiers. RESULTS: The recently approved anti-RA agents are all indicated in combination with methotrexate (MTX) for treating adults with active RA who have responded inadequately to disease-modifier drugs (DMARDs). The add-on design was frequently used in registration studies. For infliximab, etanercept, adalimumab and rituximab, add-on trials contributed, together with parallel-group trials, to gaining the approval as combination therapy. Anakinra and abatacept were authorised on the basis of add-on trial results only. CONCLUSIONS: Add-on trials do not allow assessment of the intrinsic efficacy and safety of new agents and their value as alternatives to available treatments. The indications granted for the new anti-RA agents do not specify whether newer drugs can replace standard treatments in nonresponders, can do better in the overall patient population or can be used as first-line treatment.
18705832 Case of linear immunoglobulin A bullous dermatosis associated with acquired hemophilia. 2008 Jul Linear immunoglobulin (Ig)A bullous dermatosis is a rare autoimmune subepidermal bullous dermatosis caused by circulating IgA autoantibodies directed against the antigens at the basement membrane zone. Most linear IgA bullous dermatosis cases are idiopathic, but some are associated with the use of certain drugs, infections, lymphoproliferative disorders, internal malignancies, autoimmune disorders, collagen diseases or, very rarely, other skin diseases, including autoimmune bullous diseases. Acquired hemophilia is also rare; it is a coagulation disease caused by anti-factor VIII IgG antibodies. Acquired hemophilia has been reported to be associated with malignant tumors, pregnancy or postpartum, drug reactions, collagen diseases such as rheumatoid arthritis, autoimmune disorders, and skin diseases such as psoriasis and pemphigus. We report a case of hemophilia acquired during the course of linear IgA bullous dermatosis and review reported cases of autoimmune bullous dermatoses associated with acquired hemophilia.
18642053 Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts. 2008 Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the articular synovial tissues. Although the etiology of RA has not yet been elucidated, physical and biochemical inhibition of synovial hyperplasia, which is the origin of articular destruction, may be an effective treatment for RA. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of RA. The mechanism of action of NSAIDs generally involves the inhibition of cyclooxygenase (COX) at sites of inflammation. Thus, NSAIDs were not generally considered to have a so-called anti-rheumatic effect, including inhibition of progressive joint destruction and induction of remission. However, certain conventional NSAIDs and celecoxib, a selective COX-2 inhibitor, have been reported to inhibit synovial hyperplasia by inducing the apoptosis of human synovial fibroblasts. Therefore, it has been suggested that such NSAIDs may not only have an anti-inflammatory effect but also an anti-rheumatic effect. In this review, we summarize findings about the pro-apoptotic effect, in other words, anti-proliferative effect of NSAIDs on synovial fibroblasts from patients with RA.
18625650 Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune diseases 2008 Aug We retrospectively analysed the prevalence and clinical features associated to anti-Ku antibodies in patients affected by different autoimmune diseases. Anti-Ku antibodies are detected in 147 sera out of 7239 anti-ENA positive sera (2%). They are found in 2% of patients with systemic sclerosis (SSc) (8 out of 379), 1.8% of systemic lupus erythematosus (SLE) (7 out of 372) and 1.8% of undifferentiated connective tissue disease (UCTD) (9 out of 496) and more rarely in Sjögren Syndrome and rheumatoid arthritis. Most of anti-Ku positive patients were affected by UCTD and overlap syndromes, including polymyositis, SSc and SLE. Interstitial lung disease, myositis, articular symptoms, Raynaud's phenomenon and sicca represents the main clinical features detected in our cohort. The rate and severity of pulmonary disease is similar to those found in other SSc patients. Isolated anti-Ku were detected in about 47% of sera. No clinical differences were observed between these patients and subjects with multiple anti-nuclear specificities. However, anti-Ku are usually detected in association with other serological markers in SLE and Sjögren Syndrome, while they occurred isolated in SSc and polymyositis.
18541233 Search for a functional glucocorticoid receptor in the mammalian lens. 2009 Feb Prolonged glucocorticoid treatment of medical conditions such as rheumatoid arthritis or asthma can lead to the formation of a posterior subcapsular cataract as a negative side effect. Currently, the only treatment for this cataract is surgery because very little is known about the mechanism of glucocorticoid action in the mammalian lens. Understanding of a lens glucocorticoid response is essential for the treatment and prevention of a steroid induced cataract. It has been suggested that glucocorticoids exert their effects on the lens indirectly, non-specifically, or through non-classical mechanisms. While these modes of action may contribute to the formation of glucocorticoid induced posterior subcapsular cataract, the finding of a classical, specific, functional lens glucocorticoid receptor suggests that glucocorticoids target lens epithelial cells directly, specifically, and similar to what has been observed in other cells types. This review explores the discovery of the glucocorticoid receptor in humans lens epithelial cells and the lens specific glucocorticoid response. The distinct changes in lens epithelial cell signaling pathways (MAPK and PI3K-AKT) suggest that glucocorticoids modulate several cellular functions and may explain why a lens glucocorticoid response has been difficult to elucidate.
18483467 A lipid-derived endogenous inducer of COX-2: a bridge between inflammation and oxidative s 2008 May 31 Several lines of evidence indicate that the oxidative modification of protein and the subsequent accumulation of the modified proteins have been found in cells during aging, oxidative stress, and in various pathological states including premature diseases, muscular dystrophy, rheumatoid arthritis, and atherosclerosis. The important agents that give rise to the modification of a protein may be represented by reactive aldehydic intermediates, such as ketoaldehydes, 2-alkenals and 4-hydroxy-2-alkenals. These reactive aldehydes are considered important mediators of cell damage due to their ability to covalently modify biomolecules, which can disrupt important cellular functions and can cause mutations. Furthermore, the adduction of aldehydes to apolipoprotein B in low-density lipoproteins (LDL) has been strongly implicated in the mechanism by which LDL is converted to an atherogenic form that is taken up by macrophages, leading to the formation of foam cells. During the search for an endogenous inducer of cyclooxygenase-2 (COX-2), an inducible isoform responsible for high levels of prostaglandin production during inflammation and immune responses, 4-hydroxy-2-noennal (HNE), one of the most representative lipid peroxidation product, has been identified as the potential inducer of COX-2. In addition, the following study on the molecular mechanism of the COX-2 induction by HNE has unequivocally established that a serum component, which is eventually identified to be denatured LDL, is essential for COX-2 induction. Here I review current understanding of the mechanisms by which HNE in cooperation with the serum component activates gene expression of COX-2.
18466537 A new score statistic to test for association given linkage in affected sibling pair-contr 2007 To detect association of the DR1 allele with rheumatoid arthritis (RA) given linkage in the affected sibling pairs of the replicates of Problem 3 of Genetic Analysis Workshop 15 (GAW15), we propose a new score statistic that takes into account the linkage information. We knew the answers. Linkage studies are often followed by case-control association studies of candidate genes located under the peak to identify the causes of a linkage peak. One strategy is to type the affected sibling pairs from the original linkage study and a set of unrelated controls for single-nuclear polymorphisms describing the genetic variation of these genes. For this affected sibling pair-control design, we propose a relative-risk model for the relationship between the disease outcomes of sibling pairs and their genotypes and identity-by-descent status at the locus of interest. From this model, we derive a score statistic to analyze genetic association given linkage. We compare the performance of the new statistic to the method of Li et al. and to a standard association analysis that neglects the information on the identity-by-descent status of the sibling pair. We conclude that for the GAW15 data the new method performs well and that methods that use the linkage information may be more efficient than standard comparisons of genotypes in cases and controls.
18446015 [A case of polyarteritis nodosa successfully treated by rituximab]. 2008 Apr A 47-year-old man was admitted to our hospital in January, 2006 because of a huge cutaneous ulcer in his lower limb. He was diagnosed with polyarteritis nodosa due to the cutaneous ulcer, mononeuritis multiplex, muscular pain, elevated serum CRP level and from histological findings of a skin biopsy. He was initially treated with 60 mg/day of prednisolone, followed by 1000 mg/day of intravenous cyclophosphamide (IVCY) therapy. In June, skin grafting to the cutaneous ulcer was carried out, although the graft did not survive. He revealed therapy-resistance to high dose corticosteroid and IVCY therapy, and so was treated with intravenous high dose immunoglobulin therapy. Serum CRP level then decreased and in October skin grafting was once again undertaken, this time the graft successfully survived. In December, serum CRP level increased again and cutaneous ulcer relapsed, thus he was treated with leukocyte apheresis therapy, although it was ineffective. In February 2007, he subsequently received rituximab (375 mg/m(2)/week x 3). Then, serum CRP level decreased rapidly, and cutaneous ulcer also improved. Recently the efficacy of rituximab against rheumatoid arthritis, systemic lupus erythematosus, polymyositis/dermatomyositis and ANCA-associated vasculitis has been recognized. This case suggests that rituximab is also effective against corticosteroid-resistant polyarteritis nodosa.