<i>Introduction.</i> Dysfunction of the B lymphocyte is considered to be involved in the pathogenesis of lupus nephritis (LN). Intrarenal B cells have been found in several forms of inflammatory kidney disease. B-cell activating factor (BAFF) regulates B lymphocyte proliferation and survival, and contributes to human autoimmune disease. Their role in renal inflammation is not well defined. <i>Methods.</i> Clinical parameters and renal biopsies from 62&#x2009;LN patients were prospectively analyzed. We performed standard immunohistochemistry on serial paraffin tissue sections using monoclonal antibodies to CD20 and BAFF to investigate the characteristics and significance of locally infiltrating B cells and local BAFF expression in patients with LN. <i>Results.</i> Intrarenal B cells and/or BAFF were mainly distributed in the renal interstitium. Compared to the LN-non-B-cell/BAFF expression group, proteinuria (g/24 hour), blood urea nitrogen, serum creatinine levels, LN renal activity, and chronicity indices, were all significantly greater in the LN-B-cell/BAFF expression groups. The expression of BAFF was strongly associated with the quantity of B-cell infiltrate in the interstitium. <i>Conclusion.</i> As BAFF expression was strongly associated with B-cell infiltration, we hypothesize that altered B-cell differentiation and tolerance induced by excess BAFF may be central to the pathogenesis of LN.

Chuan-Yin Sun

Yan Shen

Xiao-Wei Chen

Yu-Cheng Yan

Feng-Xia Wu

Ming Dai

Ting Li

Cheng-De Yang

The Characteristics and Significance of Locally Infiltrating B Cells in Lupus Nephritis and Their Association with Local BAFF Expression

<i>Objectives</i>. This study was conducted to clarify whether or not Tregs are involved in the development of immune-mediated pancreatitis in MRL/Mp mice as an AIP (autoimmune pancreatitis) model, in order to understand more clearly the pathogenic mechanism of AIP. <i>Methods</i>. We compared the immunohistochemical features of pancreatic forkhead box P3 (Foxp3) in the administration of poly I:C in MRL/Mp mice and two types of control mice (BALB/c and C57BL/6). As a contrast, we analyzed three mouse models of pancreatitis without autoimmune mechanism (Cerulein-, Ligation-, and Ligation + Cerulein-treated mice). After staining these specimens, we compared the ratios of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono). <i>Results</i>. Our immunohistochemical study of Foxp3 revealed that the infiltration of Foxp3-positive cells increased in poly I:C-treated MRL/Mp mice. The histopathological score of pancreatitis showed no difference among poly I:C-treated MRL/Mp, Ligation-, and Ligation + Cerulein-treated mice; however, the Foxp3/Mono ratio in poly I:C-treated MRL/Mp mice was significantly increased compared with Ligation- and Ligation + Cerulein-treated mice. <i>Conclusions</i>. MRL/Mp mice treated with poly I:C showed early development of pancreatitis with abundant infiltration of Foxp3-positive cells. There may be a possibility that Tregs are involved in the development of pancreatitis in these mice.

Masanori Koyabu

Kazushige Uchida

Yutaku Sakaguchi

Norimasa Fukata

Takeo Kusuda

Hideaki Miyoshi

Katsunori Yoshida

Kimi Sumimoto

Toshiyuki Mitsuyama

Toshiro Fukui

Akiyoshi Nishio

Kazuichi Okazaki

Possible Involvement of Foxp3<sup>+</sup> Regulatory T Cells in the Development of Immune-Mediated Pancreatitis in MRL/Mp Mice Treated with Polyinosinic:Polycytidylic Acid

Some patients with autoimmune pancreatitis (AIP) form pancreatic stones suggestive of transformation into chronic pancreatitis (CP). The present study examined the underlying risk factors and mechanism of AIP progression to confirmed CP. We compared the clinical and laboratory parameters of subjects who progressed to confirmed CP with those of the subjucts who did not in a cohort of 73 type 1 AIP patients. A total of 16 (22&#x25;) AIP patients progressed to CP. Univariate analysis revealed that relapse was significantly more frequent in the progression group, and multivariate analysis indicated that pancreatic head swelling (OR 12.7, <svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M1" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g>

		
	
</svg>) and nonnarrowing of the main pancreatic duct in the pancreatic body (OR 12.6, <svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M2" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g>

		
	
</svg>) were significant independent risk factors for progression to CP. Kaplan-Meier testing showed that the progression rate to CP was approximately 10&#x25; at 3 years and 30&#x25; at 10 years in total AIP patients and 30&#x25; at 3 years and 60&#x25; at 10 years in subjects with both risk factors. AIP with pancreatic head swelling and a history of relapse may cause pancreatic juice stagnation and nonnarrowing of the main pancreatic duct in the pancreatic body, which can progress to advanced stage chronic pancreatitis.

Masahiro Maruyama

Norikazu Arakura

Yayoi Ozaki

Takayuki Watanabe

Tetsuya Ito

Suguru Yoneda

Masafumi Maruyama

Takashi Muraki

Hideaki Hamano

Akihiro Matsumoto

Shigeyuki Kawa

Type 1 Autoimmune Pancreatitis Can Transform into Chronic Pancreatitis: A Long-Term Follow-Up Study of 73 Japanese Patients

<i>Overview</i>. The GiACTA trial is a multicenter, randomized, double-blind, and placebo-controlled study designed to test the ability of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, to maintain disease remission in patients with giant cell arteritis (GCA). <i>Design</i>. Approximately 100 centers will enroll 250 patients with active disease. The trial consists of a 52-week blinded treatment phase followed by 104 weeks of open-label extension. Patients will be randomized into one of four groups. Group A (TCZ 162 mg weekly plus a 6-month prednisone-taper); group B (TCZ 162 mg every other week plus a 6-month prednisone-taper); group C (placebo plus a 6-month prednisone-taper); and group D (placebo plus a 12-month prednisone taper). We hypothesize that patients assigned to TCZ in addition to a 6-month prednisone course are more likely to achieve the primary efficacy endpoint of sustained remission (SR) at 52 weeks compared with those assigned to a 6-month prednisone course alone, thus potentially minimizing the long-term adverse effects of corticosteroids. <i>Conclusion</i>. GiACTA will test the hypothesis that interference with IL-6 signaling exerts a beneficial effect on patients with GCA. The objective of this paper is to describe the design of the trial and address major issues related to its development.

Sebastian H. Unizony

Bhaskar Dasgupta

Elena Fisheleva

Lucy Rowell

Georg Schett

Robert Spiera

Jochen Zwerina

Olivier Harari

John H. Stone

Design of the Tocilizumab in Giant Cell Arteritis Trial

This paper assessed the burden of adverse events (AEs) associated with azathioprine (AZA), cyclophosphamide (CYC), mycophenolate mofetil (MMF), methotrexate (MTX), and cyclosporine (CsA) in patients with systemic lupus erythematosus (SLE). Thirty-eight publications were included. Incidence of AEs ranged from 42.8&#x25; to 97.3&#x25;. Common AEs included infections (2.4&#x2013;77&#x25;), gastrointestinal AEs (3.2&#x2013;66.7&#x25;), and amenorrhea and/or ovarian complications (0&#x2013;71&#x25;). More hematological cytopenias were associated with AZA (14 episodes) than MMF (2 episodes). CYC was associated with more infections than MMF (40&#x2013;77&#x25; versus 12.5&#x2013;32&#x25;, resp.) or AZA (17&#x2013;77&#x25; versus 11&#x2013;29&#x25;, resp.). Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32&#x2013;36&#x25; versus 3.6&#x2013;6&#x25;, resp.) or AZA (32&#x2013;71&#x25; versus 8&#x2013;18&#x25;, resp.). Discontinuation rates due to AEs were 0&#x2013;44.4&#x25; across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

A. Oglesby

A. J. Shaul

T. Pokora

C. Paramore

L. Cragin

G. Dennis

S. Narayanan

A. Weinstein

Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

<i>Objectives</i>. To validate van der Helm-van Mil score  (vHvM) and new ACR/EULAR criteria for the diagnosis of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). <i>Patients and Methods</i>. Adult patients with UA (swelling &#x2265;2 joints of less than 6 months duration, without diagnosis, and never treated with disease modifying drugs). <i>Results</i>. Ninety-one patients were included. Mean age: 55.6 years (SD: 17.4), 74&#x25; females. Median symptoms duration was 2 months (IR: 1&#x2013;4 months). Mean van der Helm-van Mil score was 6.9 (SD: 2). After a mean followup of 6.2 months (SD: 6), 40.7&#x25; patients fulfilled ACR 1987 RA classification criteria, 28.6&#x25; fulfilled other diagnostic criteria, and 31&#x25; remained as UA. Receiver operator characteristic curve's (ROC's) area under the curve (AUC) for the vHvM score for diagnosis of RA was 0.83.  A cutoff value of 6.94 showed sensitivity of 81&#x25; and 79.7&#x25; specificity. For the new ACR/EULAR criteria, the ROC AUC was 0.93, and a value equal to or greater than 6 showed 86.5&#x25; sensitivity and 87&#x25; specificity. <i>Conclusion</i>. van der Helm-van Mil prediction score and the new ACR/EULAR criteria proved to be valuable for the diagnosis of RA in patients with early UA.

Zaida Bedran

Cristian Quiroz

Javier Rosa

Luis J. Catoggio

Enrique R. Soriano

Validation of a Prediction Rule for the Diagnosis of Rheumatoid Arthritis in Patients with Recent Onset Undifferentiated Arthritis

<i  >Objectives</i>. To explore health care costs associated with ankylosing spondylitis (AS) in Turkey. <i  >Methods</i>. Research-identified data from a system that processes claims for all Turkish health insurance funds were analyzed. Adult prevalent and incident AS patients with two AS visits at least 60 days apart, identified between June 1, 2010 and December 31, 2010, with at least 1 year of continuous health plan enrollment for the baseline and follow-up years were included in the study. Pharmacy, outpatient, and inpatient claims were compiled over the study period for the selected patients. Generalized linear models were used to estimate the expected annual costs, controlling for baseline demographic and clinical characteristics. <i  >Results</i>. A total of 2.986 patients were identified, of which 603 were incident cases and 2.383 prevalent cases. The mean ages were 39 and 41 years, respectively, and 44&#x25; and 38&#x25; were women for incident and prevalent cases. Prevalent patients had higher comorbidity scores (5.01 versus 2.24, <svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M1" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g>

		
	
</svg>) and were more likely to be prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) (77&#x25; versus 72&#x25;, <svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M2" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><use xlink:href="#x31"/></g>

		
	
</svg>) or biologics (35&#x25; versus 8&#x25;, <svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M3" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g>

		
	
</svg>) relative to incident patients. Seventy-seven percent of prevalent patients were prescribed NSAIDs, followed by biologic and disease-modifying antirheumatic drugs (DMARDs). Total annual medical costs for incident AS patients were &#x20ac;2.253 and &#x20ac;4.233 for prevalent patients. Pharmacy costs accounted for a significant portion of total costs (88&#x25; for prevalent patient, 77&#x25; for incident patient), followed by physician office visit costs. Prior comorbidities and treatment type also significantly contributed to overall costs. 
<i  >Conclusion</i>. Annual expenditures for AS patients in Turkey were comparable relative to European countries. Pharmaceutical expenditures cover a significant portion of the overall costs. Comparative effectiveness studies are necessary to further decrease health care costs of AS treatment.

Onur Baser

Abdulkadir Burkan

Erdem Baser

Rasim Koselerli

Emre Ertugay

Akif Altinbas

Health Care Costs Associated with Ankylosing Spondylitis in Turkey: An Analysis from Nationwide Real-World Data

John K. C. Chan

Vikram Deshpande

Hisanori Umehara

Yoh Zen

IgG4-Related Disease

About this journal

<p><em>International Journal of Rheumatology</em>&nbsp;publishes original research articles and&nbsp;review articles on paediatric and adult rheumatological and musculoskeletal conditions, including topics such as basic research, therapy, surgery, and imaging.</p>


Journal profile

Meet the editorial board

<p><em>International Journal of Rheumatology</em>&nbsp;maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.</p>


Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Special Issues

Author guidelines

Editorial board

Databases and indexing

International Journal of Rheumatology - Table of contents 2013

International Journal of Rheumatology | Hindawi

title

International Journal of Rheumatology publishes original research articles and review articles on paediatric and adult rheumatological and musculoskeletal conditions, including topics such as basic research, therapy, surgery, and imaging.

description

https://images.hindawi.com/journals/ijr/ijr.banner.jpg

twitter:card

twitter:description

twitter:site

twitter:title

twitter:url

twitter:image