Sage Journals: Discover world-class research

Abstract

Background:

Rheumatoid arthritis (RA) is complicated with interstitial lung disease (ILD). Gastroesophageal reflux disease is prevented by Helicobacter pylori infection and is a predisposing factor for idiopathic pulmonary fibrosis. However, the prevalence of H. pylori infection in RA patients with ILD has not been sufficiently investigated.

Objective:

In this study, we analyzed anti-H. pylori antibodies in RA patients with ILD.

Design:

Case-control observational study

Methods:

Anti-H. pylori antibodies were analyzed in the sera of RA patients using a commercially available enzyme-linked immunosorbent assay kit.

Results:

The positivity of anti-H. pylori antibodies in RA with ILD (n = 30 [18.0%], P = .0227), usual interstitial pneumonia (n = 10 [14.3%], P = .0212), and airway disease (n = 30 [18.0%], P = .0227) was significantly lower than that of RA without chronic lung disease (n = 78 [27.5%]). The positivity of anti-H. pylori antibodies was also lower in RA with chronic lung disease (n = 68 [18.2%], P = .0059). Multiple logistic regression analyses showed that the presence of anti-H. pylori antibodies was independently and protectively associated with chronic lung disease in RA.

Conclusion:

The seroprevalence of H. pylori was lower in RA with ILD. H. pylori infection prevented ILD in patients with RA by protecting them from gastroesophageal reflux disease.

Keywords

Rheumatoid arthritis interstitial lung disease seroprevalence gastroesophageal reflux disease

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of synovial joints;¹ although the pathogenesis of RA is unknown, it is believed to involve genetic and environmental factors. RA is complicated with extra-articular manifestations including chronic lung diseases (CLD), pleuritis, pericarditis, or vasculitis. CLD in RA mainly includes airway disease (AD), interstitial lung disease (ILD), and emphysema.² The complication of ILD or AD in RA confers a poor prognosis on the patient.^3
-7 Thus, it is necessary to elucidate risk factors for ILD or AD in RA.

Helicobacter pylori is a gram-negative bacterium and childhood infections persist unless eradication is conducted. Chronic gastric infection by H. pylori causes peptic ulcers,⁸ gastric adenocarcinoma,⁹ and lymphoma.¹⁰ However, H. pylori infection reduced the risk of asthma,¹¹ gastroesophageal reflux disease,^12,13 and cardiovascular disease.^14,15 H. pylori infection might also influence the risk of autoimmune diseases including RA, although this is still controversial.^16
-23 It was suggested that the eradication of H. pylori might reduce the severity of RA.^24,25 Although gastroesophageal reflux disease is a risk factor for idiopathic pulmonary fibrosis,^26
-29 the prevalence of H. pylori in idiopathic pulmonary fibrosis was comparable.^30,31 Furthermore, the prevalence of H. pylori in patients with AD or chronic obstructive pulmonary disease was increased.^32
-34 This study aims to investigate the seroprevalence of H. pylori in RA with ILD.

Of note, the prevalence of H. pylori infection in the young is decreasing in industrialized countries, resulting in a reduced incidence of gastric cancer.^35
-37 Higher anti-H. pylori antibody levels have been detected in sera from H. pylori-infected individuals, and anti-H. pylori antibody levels were decreased several months after eradication by antimicrobial therapy.³⁸ Thus, the measurement of serum anti-H. pylori antibodies can be used to reflect H. pylori infection. However, there are few reports on the seroprevalence of H. pylori in RA with ILD. In the present study, we investigated the seroprevalence of H. pylori in RA with ILD.

Material and Methods

Patients

A total of 657 patients with RA and 52 healthy controls (healthy individuals, mean age ± standard deviation: 35.4 ± 11.1, male number: 2 [3.8%], no matching or selection was performed.) were recruited at NHO Sagamihara National Hospital, NHO Tokyo National Hospital, NHO Miyakonojo Medical Center, NHO Himeji Medical Center, NHO Nagoya Medical Center, and NHO Nagasaki Medical Center. All the patients with RA fulfilled the Rheumatoid Arthritis Classification Criteria³⁹ or American College of Rheumatology criteria for RA.⁴⁰ RA patients with computed tomography images were recruited. A diagnosis of usual interstitial pneumonia (UIP, irregular linear opacities and honeycombing), nonspecific interstitial pneumonia (NSIP, bilateral ground-glass attenuation patterns predominantly in subpleural and basal regions), AD (centrilobular or peribronchial nodules, branching linear structures, bronchial dilatation, bronchial wall thickening, or atelectasis), emphysema (low attenuation area or bullae), or no CLD [CLD(−), no abnormalities in computed tomography images] was determined based on the predominant findings of chest computed tomography images of RA patients.^41
-43 The CLD(+) group included patients with UIP, NSIP, AD, and emphysema. The ILD group included patients with UIP and NSIP. Steinbrocker stages of the RA patients were evaluated as previously described.⁴⁴ Because the collection of the sera was not conducted in the same year and the seroprevalence of H. pylori in the young generations is decreasing, birth year was used in the analyses.

This study was conducted in accordance with the principles expressed in the Declaration of Helsinki and was approved by the Research Ethics Committees of NHO Tokyo National Hospital (190010, 29 May 2019), NHO Sagamihara National Hospital, and the Central Institutional Review Board of the National Hospital Organization. Written informed consent was obtained from each participant.

Measurement of serum anti-H. pylori antibodies

Serum anti-H. pylori antibodies were detected by a commercially available enzyme-linked immunosorbent assay (ELISA) kit (E plate ‘Eiken’ H. pylori antibody II, Eiken Chemical Co., Ltd., Tokyo, Japan), according to the manufacturer’s instructions. The recommended cut-off level of the kit is 10 U/mL. The standard anti-H. pylori antibodies (3, 10, 30, 100 U/mL) and the horseradish peroxidase-labeled mouse anti-human IgG monoclonal antibody were used in the ELISA kit (https://www.info.pmda.go.jp/downfiles/ivd/PDF/170005_22200AMX00935000_A_01_03.pdf).

Statistical analysis

The presence of anti-H. pylori antibodies was compared with CLD(−) RA patients by Fisher’s exact test using 2 × 2 contingency tables. The clinical characteristics of RA patients with or without anti-H. pylori antibodies were compared by Student’s t-test or Fisher’s exact test using 2 × 2 contingency tables. Multiple logistic regression analysis was conducted to evaluate whether the presence of anti-H. pylori antibodies was independently associated with CLD or RA from other clinical information, including birth year, sex, Steinbrocker stage, and smoking status. Statistical significance was considered to be two-sided P-values less than .05.

Results

Detection of anti-H. pylori antibodies in RA patients and controls

Titers of anti-H. pylori antibodies were measured in the sera of RA patients (Figure 1). The presence of anti-H. pylori antibodies in each group was compared with those in CLD(−) RA patients (Table 1). The positivity of anti-H. pylori antibodies in RA with ILD (n = 30 [18.0%], P = .0227), UIP (n = 10 [14.3%], P = .0212), and AD (n = 30 [18.0%], P = .0227) was significantly lower than that in CLD(−) (n = 78 [27.5%]). The positivity of anti-H. pylori antibodies was also lower in RA with CLD (n = 68 [18.2%], P = .0059). Anti-H. pylori antibody levels in RA with CLD were also analyzed by Student’s t-test and were lower when compared with CLD(−) RA (mean ± SD, 7.3 ± 12.2 vs 10.6 ± 16.4 U/mL, P = .0048). Thus, the positivity of anti-H. pylori antibody was lower in RA with ILD, UIP, AD, or CLD.

Figure 1.

Anti-H. pylori antibody levels in RA patients and controls.

Table 1.

The positivity of anti-H. pylori antibody in RA patients.

	n	Anti-H. pylori antibody positive, n (%)	P-value
ILD	167	30 (18.0)	.0227
UIP	70	10 (14.3)	.0212
NSIP	97	20 (20.6)	.2259
AD	167	30 (18.0)	.0227
Emphysema	39	8 (20.5)	.4416
CLD(+)	373	68 (18.2)	.0059
CLD(−)	284	78 (27.5)
Total RA	657	146 (22.2)

Abbreviations: AD, airway disease; CLD, chronic lung disease; ILD, interstitial lung disease; NSIP, nonspecific interstitial pneumonia; RA, rheumatoid arthritis; UIP, usual interstitial pneumonia.

ILD group includes UIP and NSIP groups. The CLD(+) group includes UIP, NSIP, AD, and emphysema patients. The positive number in each group is shown. Percentages are shown in parentheses. Differences compared with the CLD(−) population were tested by Fisher’s exact test using 2 × 2 contingency tables.

Clinical characteristics of RA patients with or without anti-H. pylori antibodies

A potential association of the clinical characteristics of RA patients with the presence of anti-H. pylori antibodies was analyzed (Table 2). CLD was associated with the absence of anti-H. pylori antibodies (P = .0059) whereas other clinical manifestations were not associated with the presence or absence of anti-H. pylori antibodies.

Table 2.

Association of anti-H. pylori antibody positivity with the clinical characteristics of RA.

Clinical manifestations	Total RA (n = 657)	Anti-H. pylori antibody (+) RA (n = 146)	Anti-H. pylori antibody (−) RA (n = 511)	P-value
Age, years (SD)	65.4 (11.1)	65.0 (9.8)	65.5 (11.5)	*.5483
Birth year, years (SD)	1947 (10.6)	1946 (9.7)	1947 (10.9)	*.3937
Male n (%)	155 (23.6)	29 (19.9)	126 (24.7)	.2691
Age at onset, years (SD)	52.3 (15.0)	53.2 (14.2)	52.1 (15.2)	*.4234
Steinbrocker stage 3, 4, n (%)	318 (49.5)	61 (42.4)	257 (51.5)	.0586
Underweight (body mass index <18.5 kg/m²), n (%)	494 (82.1)	121 (87.7)	373 (80.4)	.0576
Smoker or past smoker, n (%)	239 (39.6)	59 (42.8)	180 (38.7)	.5448
CLD (+), n (%)	373 (56.8)	68 (46.6)	305 (59.7)	.0059
Rheumatoid factor positive, n (%)	567 (86.3)	123 (84.2)	444 (86.9)	.4146
Anti-citrullinated peptide antibody positive, n (%)	592 (90.1)	134 (91.8)	458 (89.6)	.5305
Krebs von den lungen-6 positive, n (%)	115 (25.4)	21 (24.1)	94 (25.8)	.8911
Surfactant protein-D positive, n (%)	98 (25.3)	17 (22.7)	81 (26.0)	.6577

Abbreviations: CLD, chronic lung disease; RA, rheumatoid arthritis; SD, standard deviation.

The CLD(+) group includes usual interstitial pneumonia, nonspecific interstitial pneumonia, airway disease, and emphysema patients. The number or mean of each group is shown. Percentages or SDs are shown in parentheses. Differences between anti-H. pylori antibody(+) and (−) RA populations were tested with Student’s t-test or Fisher’s exact test using 2 × 2 contingency tables.

Student’s t-test was used.

Multiple logistic regression analysis of anti-H. pylori antibodies

Multiple logistic regression analysis was conducted to exclude the influence of clinical characteristics on the protective association of the presence of anti-H. pylori antibodies with CLD (Table 3). In univariate analysis, the presence of anti-H. pylori antibodies was significantly associated with CLD (P = .0050, odds ratio [OR] 0.59, 95% confidence interval [CI] 0.41, 0.85). The association of the presence of anti-H. pylori antibodies remained significant (P_adjusted = .0022, OR_adjusted 0.53, 95% CI 0.35, 0.79), when conditioned on the other clinical characteristics. Thus, this suggested that the presence of anti-H. pylori antibodies was independently and protectively associated with CLD in RA.

Table 3.

Multiple logistic regression analysis of anti-H. pylori antibody positivity and clinical manifestations of CLD in RA.

Clinical manifestations	Unconditioned			Conditioned on other factors
Clinical manifestations	OR	95%CI	P-value	OR_adjusted	95%CI	P _adjusted
Anti-H. pylori antibody, positive	0.59	(0.41, 0.85)	.0050	0.50	(0.33, 0.76)	.0012
Birth year, years	0.96	(0.95, 0.98)	1.03 × 10⁻⁶	0.95	(0.94, 0.97)	1.28 × 10⁻⁷
Male	1.83	(1.25, 2.67)	.0019	1.32	(0.84, 2.08)	.2239
Steinbrocker stage	0.84	(0.74, 0.95)	.0073	0.83	(0.72, 0.96)	.0141
Smoking status	1.41	(1.13, 1.76)	.0025	1.53	(1.20, 1.96)	.0006

Abbreviations: CI, confidence interval; CLD, chronic lung diseases; OR, odds ratio; RA, rheumatoid arthritis.

P, OR, 95%CI, P_adjusted, and OR_adjusted were calculated by logistic regression analysis on RA patients.

Comparison of the presence of anti-H. pylori antibodies between RA patients and controls

The presence of anti-H. pylori antibodies was compared between RA patients and healthy controls (Supplementary Table S1), and no difference was revealed. In order to exclude the effects of other clinical features including birth year and sex on the association between the presence of anti-H. pylori antibodies and RA, multiple logistic regression analysis was conducted, and no association was detected. Thus, no association was observed between the presence of anti-H. pylori antibodies and RA.

Discussion

In this study, the positivity of anti-H. pylori antibodies in RA with ILD, UIP, and AD was lower compared with RA without CLD. We also revealed that the presence of anti-H. pylori antibodies was independently and protectively associated with CLD in RA. However, the presence of anti-H. pylori antibodies was not associated with RA, per se.

In some previous studies, the prevalence of H. pylori infection was comparable between RA patients and healthy individuals.^16
-18,45 However, it was decreased in another study.²² Furthermore, H. pylori infection increased the risk of RA in women less than 30 years old.²³ In the present study, the seroprevalence of H. pylori in RA was similar to that in healthy individuals, suggesting no association between H. pylori infection and RA, per se.

It is known that H. pylori infection prevents gastroesophageal reflux disease by decreasing gastric acid secretion.^12,13 Gastroesophageal reflux disease with microaspiration was revealed to be a predisposing factor for idiopathic pulmonary fibrosis.^26,27 Thus, the prevalence of H. pylori in idiopathic pulmonary fibrosis was estimated to be lower; however, it was not significantly lower than that in healthy controls, though there was a lower trend.^30,31 In our study, the seroprevalence of H. pylori in RA patients with ILD was significantly lower compared with RA without CLD. Thus, H. pylori infection might prevent the development of ILD in RA probably by protecting patients from gastroesophageal reflux disease.

The prevalence of H. pylori in patients with AD was increased in previous studies.^32,33 However, in this study, the seroprevalence of H. pylori in RA patients with AD was significantly lower compared with RA without CLD. These data suggested that the pathogenesis of AD in RA is different from that in AD without RA.

It was reported that the prevalence of H. pylori infection was influenced by birth year^36,37 suggesting the associations between the presence of anti-H. pylori antibodies and CLD in our study could be influenced by birth year. After the effects of birth year were adjusted for in multiple logistic regression analyses, the associations between the presence of anti-H. pylori antibodies and CLD remained significant. Thus, the presence of anti-H. pylori antibody was independently and protectively associated with CLD in RA.

To the best of our knowledge, this is the first study to report the seroprevalence of H. pylori in RA patients with ILD. The results of the study indicated the lower seroprevalence of H. pylori in RA patients with ILD, UIP, AD, or CLD. This study includes some limitations. The sample size of the study was modest and this study was performed in Japanese populations. Larger-scale studies must be performed in different populations to replicate the results. Because information on gastroesophageal reflux disease in RA patients was not obtained in this study, the potential confounding effects of gastroesophageal reflux disease could not be excluded. The potential correlations between H. pylori infection, gastroesophageal reflux disease, and ILD in RA patients should be investigated in future studies with sufficient clinical information.

Conclusion

The seroprevalence of H. pylori was lower in RA with ILD. H. pylori infection prevented ILD in patients with RA by protecting them from gastroesophageal reflux disease.

Abbreviations

AD: airway disease

CLD: chronic lung diseases

ELISA : enzyme-linked immunosorbent assay

ILD: interstitial lung disease

NSIP: nonspecific interstitial pneumonia

RA: rheumatoid arthritis

UIP: usual interstitial pneumonia

Supplemental Material

sj-docx-1-bmi-10.1177_11772719241297171 – Supplemental material for Helicobacter pylori Seroprevalence in Rheumatoid Arthritis Patients with Interstitial Lung Disease

Supplemental material, sj-docx-1-bmi-10.1177_11772719241297171 for Helicobacter pylori Seroprevalence in Rheumatoid Arthritis Patients with Interstitial Lung Disease by Shomi Oka, Takashi Higuchi, Hiroshi Furukawa, Kota Shimada, Akira Okamoto, Misuzu Fujimori, Atsushi Hashimoto, Akiko Komiya, Koichiro Saisho, Norie Yoshikawa, Masao Katayama, Toshihiro Matsui, Naoshi Fukui, Kiyoshi Migita and Shigeto Tohma in Biomarker Insights

Footnotes

Acknowledgements

None.

Declarations

References

Smolen

Aletaha

McInnes

IB.

Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038.

Stainer

Tonutti

De Santis

, et al Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: a critical review. Front Med (Lausanne). 2023;10(1129939):1129939.

Hakala

Poor prognosis in patients with rheumatoid arthritis hospitalized for interstitial lung fibrosis. Chest. 1988;93(1):114-118.

Koduri

Norton

Young

, et al Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort. Rheumatology. 2010;49(8):1483-1489.

Kim

Elicker

Maldonado

, et al Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2010;35(6):1322-1328.

Vergnenegre

Pugnere

Antonini

, et al Airway obstruction and rheumatoid arthritis. Eur Respir J. 1997;10(5):1072-1078.

Swinson

Symmons

Suresh

Jones

Booth

Decreased survival in patients with co-existent rheumatoid arthritis and bronchiectasis. Br J Rheumatol. 1997;36(6):689-691.

Nomura

Stemmermann

Chyou

Perez-Perez

Blaser

MJ.

Helicobacter pylori infection and the risk for duodenal and gastric ulceration. Ann Intern Med. 1994;120(12):977-981.

Parsonnet

Friedman

Vandersteen

, et al Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127-1131.

10.

Parsonnet

Hansen

Rodriguez

, et al Helicobacter pylori infection and gastric lymphoma. N Engl J Med. 1994;330(18):1267-1271.

11.

Chen

Blaser

MJ.

Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis. 2008;198(4):553-560.

12.

Koike

Ohara

Sekine

, et al Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion. Gut. 2001;49(3):330-334.

13.

Raghunath

Hungin

Wooff

Childs

Prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease: systematic review. BMJ. 2003;326(7392):737.

14.

Mayr

Kiechl

Mendall

Willeit

Wick

Increased risk of atherosclerosis is confined to CagA-positive Helicobacter pylori strains: prospective results from the Bruneck study. Stroke. 2003;34(3):610-615.

15.

Chen

Segers

Blaser

MJ.

Association between Helicobacter pylori and mortality in the NHANES III study. Gut. 2013;62(9):1262-1269.

16.

Bartels

Pedersen

Kristensen

, et al Helicobacter pylori infection is not associated with rheumatoid arthritis. Scand J Rheumatol. 2019;48(1):24-31.

17.

Showji

Nozawa

Sato

Suzuki

Seroprevalence of Helicobacter pylori infection in patients with connective tissue diseases. Microbiol Immunol. 1996;40(7):499-503.

18.

Meron

Amital

Shepshelovich

, et al Infectious aspects and the etiopathogenesis of rheumatoid arthritis. Clin Rev Allergy Immunol. 2010;38(2-3):287-291.

19.

Smyk

Koutsoumpas

Mytilinaiou

Rigopoulou

Sakkas

Bogdanos

DP.

Helicobacter pylori and autoimmune disease: cause or bystander. World J Gastroenterol. 2014;20(3):613-629.

20.

Wang

Cao

Zhang

, et al Helicobacter Pylori and autoimmune diseases: involving multiple systems. Front Immunol. 2022;13(833424):833424.

21.

Etchegaray-Morales

Jiménez-Herrera

Mendoza-Pinto

, et al Helicobacter pylori and its association with autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis and Sjögren syndrome. J Transl Autoimmun. 2021;4(100135):100135.

22.

Tanaka

Singh

Saito

, et al Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan. Mod Rheumatol. 2005;15(5):340-345.

23.

Lee

Liao

Lin

Wei

JC.

Influence of Helicobacter pylori infection on risk of rheumatoid arthritis: a nationwide population-based study. Sci Rep. 2023;13(1):15125.

24.

Seriolo

Cutolo

Zentilin

Savarino

Helicobacter pylori infection in rheumatoid arthritis. J Rheumatol. 2001;28(5):1195-1196.

25.

Zentilin

Seriolo

Dulbecco

, et al Eradication of Helicobacter pylori may reduce disease severity in rheumatoid arthritis. Aliment Pharmacol Ther. 2002;16(7):1291-1299.

26.

Lee

Ryu

Elicker

, et al Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184(12):1390-1394.

27.

Bédard Méthot

Leblanc

Lacasse

. Meta-analysis of gastroesophageal reflux disease and idiopathic pulmonary fibrosis. Chest. 2019;155(1):33-43.

28.

Fidler

Sitzer

Shapera

Shah

PS.

Treatment of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis. Chest. 2018;153(6):1405-1415.

29.

Chen

You

Liu

Xue

Qin

Jiang

HD.

Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats. Clin Sci (Lond). 2017;131(10):951-963.

30.

Bennett

Bargagli

Refini

, et al Helicobacter pylori seroprevalence in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2014;43(2):635-638.

31.

Fahim

Dettmar

Morice

Hart

SP.

Gastroesophageal reflux and idiopathic pulmonary fibrosis: a prospective study. Medicina (Kaunas). 2011;47(4):200-205.

32.

Kanbay

Gur

Akcay

Yilmaz

Helicobacter pylori seroprevalence in patients with chronic bronchitis. Respir Med. 2005;99(10):1213-1216.

33.

Tsang

Lam

, et al High seroprevalence of Helicobacter pylori in active bronchiectasis. Am J Respir Crit Care Med. 1998;158(4):1047-1051.

34.

Gencer

Ceylan

Yildiz Zeyrek

Aksoy

Helicobacter pylori seroprevalence in patients with chronic obstructive pulmonary disease and its relation to pulmonary function tests. Respiration. 2007;74(2):170-175.

35.

Kikuchi

Nakajima

Kobayashi

, et al Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer. Jpn J Cancer Res. 2000;91(8):774-779.

36.

Ueda

Gosho

Inui

, et al Prevalence of Helicobacter pylori infection by birth year and geographic area in Japan. Helicobacter. 2014;19(2):105-110.

37.

Abiko

Hirayama

Otaki

, et al Changes in prevalence of Helicobacter pylori in Japan from 2008 to 2018: a repeated cross-sectional study. BMJ Open. 2022;12(9):e058774.

38.

Tanaka

Goto

Yamagishi

, et al Long-term response of Helicobacter pylori antibody titer after eradication treatment in middle-aged Japanese: JPHC-NEXT study. J Epidemiol. 2023;33(1):1-7.

39.

Aletaha

Neogi

Silman

, et al 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581.

40.

Arnett

Edworthy

Bloch

, et al The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315-324.

41.

Tanaka

Kim

Newell

, et al Rheumatoid arthritis-related lung diseases: CT findings. Radiology. 2004;232(1):81-91.

42.

Mori

Cho

Koga

Sugimoto

Comparison of pulmonary abnormalities on high-resolution computed tomography in patients with early versus longstanding rheumatoid arthritis. J Rheumatol. 2008;35(8):1513-1521.

43.

Oka

Furukawa

Shimada

, et al Association of human leukocyte antigen alleles with chronic lung diseases in rheumatoid arthritis. Rheumatology (Oxford). 2016;55(7):1301-1307.

44.

Steinbrocker

Traeger

Batterman

RC.

Therapeutic criteria in rheumatoid arthritis. J Am Med Assoc. 1949;140(8):659-662.

45.

Youssefi

Tafaghodi

Farsiani

Ghazvini

Keikha

Helicobacter pylori infection and autoimmune diseases; is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. J Microbiol Immunol Infect. 2021;54(3):359-369.