Association of Helicobacter pylori Infection with Systemic Lupus Erythematosus
Received Date: Oct 14, 2017 / Accepted Date: Nov 07, 2017 / Published Date: Nov 16, 2017
Objective: Systemic Lupus Erythematosus (SLE) is an autoimmune disease of unknown etiology. However, a complex combination of host and environmental factors are believed to play a pivotal role. In the pathogenesis of SLE, several infectious agents have been held responsible such as Cytomegalovirus, Parvovirus B19, Epstein Barr virus and Retrovirus. There is a variable relationship between SLE and Helicobacter, which is different from that of lupus and other infections. The aim of this study was to investigate the association between Helicobacter pylori (H.pylori) infection and SLE development.
Method: In this study, 82 serum samples and 65 stool samples were collected from the SLE patients as well as the control group, respectively. An enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of specific IgG/IgM antibodies against H.pylori in all serum samples. The presence of H.pylori antigen was examined in all stool samples by using stool antigen test. Suitable statistical analysis was applied.
Results: Thirteen (15.9%) out of 82 SLE patients and 30 (36.6%) out of 82 control group were anti-H.pylori IgM seropositive. There was a significant difference between the level of IgM in SLE patients and control group (p<0.05). Anti-H.pylori IgG antibodies were present in 37 (45.1%) of SLE patients and in 41 (50%) of the control group without any significant difference. Regarding stool antigen examination, there were 24 (36.9%) and 26 (42/6%) positive samples among the SLE patients and control group, respectively. There was no significant difference between the patients and controls samples in the number of stool antigen test positive samples (p>0.05).
Conclusions: Based on data obtained in this study, it is concluded that there was a significant difference between the number of IgM seropositive in SLE patients and control group, which shows that SLE disease may have an inhibitory role in H.pylori infection occurance.
Keywords: Systemic lupus erythematosus; Autoimmune; Infection; Helicobacter pylori ; ELISA; Antibodies; Antigen
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect any organ of the body including the skin, mucous membranes, joints, kidneys, blood and brain [1-7]. SLE is the perfect model of autoimmune disorder, begin from innate immunity to adaptive immunity and leading to loss of self-tolerance [8,9]. The exact etiology of SLE is unknown, however, several genetic and environmental factors might have a role [3,10,11]. Epidemiologic studies showed variations in the prevalence and course of SLE between genders, different ages, races and geographic locations [7,12]. The incidence of SLE is estimated to be about 5 per 100,000 people per year with a prevalence of 40 to 80 per 100,000 . Women are more frequently affected than men, with a sex ratio of approximately 9:1 between the ages of 15–45 years [1,3,12,13]. The disease is more common in Native American, African-American, Asian and Hispanic descent [2,14].
H.pylori is a gram-negative, spiral-shaped, flagellated and microaerophilic bacterium that colonizes the human gastric mucosa [19-22]. H.pylori infection is one of the most usual bacterial infections in humans. H.pylori infection is usually acquired in early childhood and continues life-long in the lack of medicine treatment [21-23]. H.pylori and humans have a lengthy period of coevolution, as long as human migration out of Africa about 60,000 years ago . The prevalence of H.pylori infection differs broadly by geographic area, age, race, and socioeconomic status [19,22,25]. The overall prevalence of this bacterium is as high as 80% in many developing countries to 20-50% in industrialized countries . H.pylori infection not only causes a several of gastrointestinal diseases including peptic ulcers, noncardia gastric adenocarcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma, but also plays a role in the pathogenesis of various autoimmune disorders such as idiopathic thrombocytopenic purpura, rheumatoid arthritis (RA), autoimmune gastric atrophy, Sjogren’s syndrome and autoimmune thyroiditis [17,27]. This extended coexistence of H.pylori in humans may be in part beneficial to humans. Because, in some instances, there is some evidences explaining a protective effect for H.pylori infection against diseases progression such as inflammatory bowel disease (IBD), multiple sclerosis (MS), SLE and allergic diseases [27,28].
There are several methods for the diagnosis of H.pylori , each with its own benefits, weaknesses and limitations . Invasive techniques based on gastric specimens for histology, culture and a rapid urease test, and non-invasive techniques based on peripheral samples, such as blood, stools, urine, saliva or breath samples, for detection of bacterial antigens, antibodies or urease activity are used to diagnosis of H.pylori infection [22,30,31]. In this study, in order to investigate the possible association between H.pylori infection and the development of SLE, the prevalence of H.pylori Infection in SLE patients compared with the healthy individuals was evaluated.
Materials and Methods
Patients and controls
Eighty-two SLE patients (76 females and 6 males) who fulfilled American college of rheumatology revised criteria for the classification of SLE were followed up at Rheumatology Clinic affiliated to Isfahan University of Medical Sciences . The demographic data such as age; gender; education; age at the SLE onset; duration of disease; history of gastrointestinal disease and previous administration of anti-H.pylori medication were recorded. Disease activity was determined by the SLE disease activity index (SLEDAI-2k) . In addition, eighty-two healthy subjects (77 females and 5 males) of matched gender were used as healthy control group. Sera of all patients and controls were obtained and stored at -20°C. Also, stool specimens at the same time with serum specimens were collected from 65 patients and controls in sterile containers and kept at -70°C.
The presence of IgM and IgG anti H.pylori antibodies in the all serum samples were determined by an enzyme-linked immunosorbent assay (ELISA) based on the manufacturer's instructions (Monobind Inc., USA). Diluted serum and reference samples were pipetted into the streptavidin coated wells and then H.pylori biotin reagent solution was added. The microplates were covered and incubated for 60 min at room temperature. The contents of the wells were discharged and washed the wells three times. Then, an enzyme anti-human IgG/IgM conjugate was added into each well. After 30 min of incubation and again washing, substrate solution was added to all wells and was incubated for 15 min at room temperature. The reaction was stopped by adding stopping solution and the microplate was read at 450 nm with a reference wavelength of 620-630 nm by ELISA reader. A positive result for IgG and IgM anti H.pylori antibodies was defined as a concentration greater than 20 U/ml and 40 U/ml respectively.
Stool antigen test
H.pylori antigen was detected in all specimens by stool antigen kit according to the manufacturer's instructions (Farafan Diagnostic kit, Inc; Iran). A little portion of stool specimen was transferred to a dropper vial containing of diluent buffer and later one minute of shaking, about one to two droplets was dispensed into the oval cavity of the test cassette. The test result was read at least after 15 min and based on the appearance of colored lines. The appearance of two purple lines C (control) and T (test) indicated that test was positive and only one purple line in C area indicated the negative result. Also, a pale colored line in T area was considered positive.
All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS version 20). The prevalence of H.pylori infection among groups was compared by chi-square testing. Quantitative data were compared by student’s t-test and described as mean ± SD. A p value of <0.05 was considered to be statistically significant for all data analyses.
The mean age of the patients and their mean duration of disease at examination were 38.35 ± 10.2 years (range: 24 to 74) and 11 ± 5 years (range: 2 to 31) respectively. The mean age at disease onset was 26.9 ± 9.8 years (range: 14 to 59 years). SLE disease activity index (SLEDAI-2k) scores ranged from 0 to 10 (mean: 1 ± 2). The frequency of important SLE manifestations (according to SLEDAI-2k) in patients was: increased DNA binding (19.5%), Rash/low complement (8.5%), arthritis (6.1%), proteinuria (4.9%), thrombocytopenia (3.7%), urinary casts/hematuria /pyuria (1.2%). The mean age of healthy control group at sampling was 42.38 ± 12.8 years (range: 18 to 68 years).
Anti-H.pylori IgG antibodies were detected in 37 (45.1%) of SLE patients and in 41 (50%) of healthy controls. There was no significant difference between the patients and controls in the number of anti- H.pylori IgG seropositive samples (p=0.53). In addition, 13 (15.9%) of SLE patients and 30 (36.6%) of the control group were seropositive for anti-H.pylori IgM antibodies. Therefore, anti-H.pylori IgM seropositivity was found significantly higher in the control group than SLE patients (p=0.003). Regarding stool antigen test, there were 24 (36.9%) H.pylori positive samples among the 65 of SLE patients and 26 (42/6%) among the 61 of healthy controls which showed no statistically significant difference between two groups (p=0.58). In general, 3 (4.6%) of SLE patients and 10 (15.3%) of the control group were positive for anti-H.pylori IgM and IgG antibodies and stool antigen test. Results are shown in Table 1.
|Group||Number of Anti-H.pylori IgM||Number of Anti-H.pylori IgG||Number of Stool antigen test|
|SLE patients||13 (15.9%)||69 (84.1%)||37 (45.1%)||45 (54.9%)||24 (36.9%)||41 (63.1%)|
|Control||30 (36.6%)||52 (63.4%)||41 (50%)||41 (50%)||26 (42.6%)||35 (57.4%)|
Table 1: The prevalence of Helicobacter pylori in SLE patients and control group
We investigated the possible associations of mean age of SLE onset, an average of disease duration, the frequency of lupus manifestations, history of gastrointestinal disease, used prescribed medications for H.pylori infection and used antibiotics between the SLE patients infected with H.pylori and H.pylori negative SLE patients. It was shown that there was no significant difference between both groups for all the above-mentioned factors (p>0.05). (Tables 2 and 3)
|Anti-H.pylori IgM||p value||Anti-H.pylori IgG||p value||Stool antigen test||p value|
|Mean age of onset of SLE||26.54||26.94||0.89||25||29.19||0.1||27.11||26.69||0.84|
|Average of disease duration||12.38||11.64||0.66||11.84||11.69||0.9||11.93||11.25||0.65|
|History of gastrointestinal disease||Yes||2||18||0.5||11||9||0.43||4||12||0.37|
|Used prescribed medications for H.pylori infection||Yes||0||8||0.34||5||3||0.45||2||5||1|
Table 2: Associations between various factors and H.pylori infection in SLE patients
|Anti-H.pylori IgM||p value||Anti-H.pylori IgG||p value||Stool antigen test||p value|
|Increase DNA binding||2||14||1||7||9||1||4||9||0.75|
Table 3: Associations between lupus manifestations and H.pylori infection in SLE patients
Autoimmune diseases affect 5-10% of the general population and are a significant cause of morbidity and mortality worldwide . The cause of these diseases such as SLE is unknown; although it might be resulted from the interaction between environmental and host factors . The association between infection and autoimmune diseases over the last twenty years has been increasingly supposed [16,27]. Several infectious agents such as Cytomegalovirus , Parvovirus B19, Epstein Barr virus and Retrovirus, might play a major role in the pathogenesis of SLE [18,34]. However, there is a different relationship between SLE and Helicobacter , from that of other infections. Amongst bacteria, H.pylori seems to play a pathogenetic role in autoimmune diseases such as autoimmune gastritis, Sjögren’s syndrome, atherosclerosis, immune thrombocytopenia purpura, inflammatory bowel diseases and autoimmune pancreatitis [15,17,27]. Also, H.pylori might have a protective role in allergic disorders [7,28], inflammatory bowel disease , asthma , immune thrombocytopenic purpura  and multiple sclerosis .
Fewer studies have conducted in order to understand a correlation between H.pylori infection and SLE. In an animal study, it was found that exposure to H.pylori urease can lead to production of anti-single stranded DNA antibodies . Kalabay and colleagues studied the prevalence of anti-H.pylori antibodies in various autoimmune rheumatic diseases and they found the comparable prevalence of H.pylori in SLE patients and healthy controls . Showji et al. showed that the titers of anti-H.pylori antibodies were lower in SLE than other autoimmune diseases . In another study, Sawalha et al. compared the prevalence of H.pylori seropositivity in 466 SLE patients to matched controls and realized SLE patients were less frequently positive (36.5%) for H.pylori as compared with healthy controls (42.9%). This negative association for African–American female SLE patients as compared with controls was even severed (38.1 versus 60.2%; p=0.0009). It was noted that H.pylori seropositive African- American females compared to H.pylori negative SLE patients prone to develop SLE at an older age. The average age of the beginning SLE in the seropositive and seronegative group was 34.4 and 28 years, respectively . The authors suggest that exposure to H.pylori may oer some protective benefit against developing SLE in this specific population. In the current study, our data showed no significant difference between the number of positive samples of anti-H.pylori IgG and stool antigen among SLE patients and healthy controls.
These studies have some limitations but nevertheless, all of them showed a negative relationship between SLE and H.pylori infection. This difference might be resulted from the study population, diversity in the prevalence of H.pylori infection in the different part of the world and laboratory methods which applied to detective it.
In conclusion, our study shows that patients with SLE had a lower prevalence of acute H.pylori infection than healthy controls and there was a negative association between H.pylori infection and SLE. Based on obtained data, it could be concluded that SLE disease might have an inhibitory role in H.pylori infection occurrence. More studies are required to elucidate the possible association between the H.pylori infection and SLE.
The authors wish to thank the University of Isfahan for their financial support. We are also thankful to the Department of Rheumatology in Alzahra Hospital and the Isfahan University of Medical Sciences.
Conflict of Interest
The authors have no conflicts of interest to declare.
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Citation: Ejtehadi A, Roghanian R, Sayyed Bonakdar Z (2017) Association of Helicobacter pylori Infection with Systemic Lupus Erythematosus. J Clin Cell Immunol 8: 528. Doi: 10.4172/2155-9899.1000528
Copyright: ©2017 Ejtehadi A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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