The anti-inflammatory effects of exercise on autoimmune diseases:A 20-year systematic review

Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

The Value of Traditional Medicine Should not be Underestimated-Traditional Chinese Medicine in Treatment of Autoimmune Diseases

Autoimmune diseases of the nervous system(ADNS)are characterized by the formation of a pronounced neurologic deficit and often lead to disability.The attention of doctors and researchers is increasingly attracted by complementary medicine as adjuvant or preventive therapy for various diseases,including autoimmune diseases.Traditional Chinese medicine(TCM)is a combination of treatment methods that include acupuncture,herbal medicine,dietetics,physical exercises,and other methods that are often used in conjunction with recognized approaches of official medical science.The article describes the application of TCM techniques in autoimmune diseases of the nervous system,and demonstrates clinical experience in the use of acupuncture,herbal medicine,diets and physical exercises.Traditional and complementary medicine is an important and often underestimated healthcare resource,especially in the prevention and treatment of autoimmune diseases of the nervous system.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases

As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Spectrum of Neurological Disorders Related to Autoimmune Diseases in Brazzaville, Congo

Background: Autoimmune diseases, which are among the leading causes of morbidity and mortality in the world, are pathologies caused by a dysfunction of the immune system. They can affect the central nervous system, the peripheral nervous system or both nervous systems. Objectives: To describe the epidemiological, clinical, paraclinical, therapeutic and evolutive aspects of neurological disorders related to autoimmune diseases. Methods: This was a prospective cohort study. It was carried out from 1 January 2015 to 31 December 2019 (5 years). It focused on patients aged 15 years and above, who were hospitalized or followed as ambulatory patients for neurological disorders related to autoimmune diseases in the neurology department of the university teaching hospital in Brazzaville. Results: Among the 41 patients who fulfilled inclusion criteria, there were 29 (70.73%) women and 12 (29.27%) men. The average age of patients was 38.3 ± 13.8 years. An increase in the frequency of neurological disorders related to autoimmune diseases was observed every year. The main neurological disorders were neuromyelitis optica spectrum disorders (n = 14;34.15%), acute polyradiculoneuropathies (n = 13;31.71%), chronic polyradiculoneuropathies (n = 4;9.75%) and acute disseminated encephalomyelitis (n = 3;7.31%). The treatments administered, which consisted of corticosteroids and immunosuppressive drugs, had significantly improved the vital prognosis and functional status of patients (p = 0.025). Conclusion: In our study population, neurological disorders related to autoimmune diseases are rare. The neurological clinico-pathological entities diagnosed are similar to those reported in the literature. The therapeutic approaches used improve the quality of life of patients.

Panorama, Reasons for Seeking Care and Evolution of Systemic Autoimmune Diseases in Benin Hospitals in 2021

Introduction: Systemic autoimmune diseases have been poorly studied in sub-Saharan Africa and their frequency is not well known. This study provided an overview of the main reasons for the use of care and their evolution in the main hospitals in Benin. Methods: This was a multi-centric descriptive cross-sectional study conducted in the internal medicine, rheumatology, dermatology and nephrology departments of nine (09) public and private hospital centers in Benin over a 57-month period, from January 1st, 2017 to September 30th, 2021. It involved patients followed for a systemic autoimmune disease. The data was collected with a digital survey sheet and then processed and analyzed with the R software (version 3.4). Results: Two hundred and three (203) patients were recorded, which represents a hospital frequency of 0.13%. The mean age was 44 years and the sex ratio (M/F) was 0.29. Connective tissue disease accounted for 95.07% of systemic autoimmune diseases which were dominated by rheumatoid arthritis (40.9%) and systemic lupus (37.4%). Ten cases of vasculitis have been reported and dominated by Behçet’s disease (40%). The main reasons for seeking care were asthenia, weight loss and fever. Arthralgia and skin lesions are the main guiding signs. Six deaths (3.1%) were recorded among connective tissue disease and 1 death (10%) among vasculitis. Conclusion: In spite of being rare, systemic autoimmune diseases are a reality in Benin. A general population study would provide a better understanding of clinical characteristics and identify prognostic factors.

Epidemiological Profile of Autoimmune Diseases in Thiès, Senegal: About a Descriptive Observational Study over 11 Years in 2 Internal Medicine Departments and a Dermatology Department

Introduction: Autoimmune diseases are characterized by a very large clinical polymorphism that can lead to a diagnostic wandering. So, we aimed to determine their epidemiological profile outside the context of Dakar (capital of Senegal) where the technical plateau is more elevated. Methodology: We conducted a retrospective descriptive and observational study from January 1, 2007 to December 31, 2017. All patients admitted or followed in outpatient in the Internal Medicine departments of the Saint Jean de Dieu and Regional Hospitals of Thiès as well as in the dermatology department of the CHRT (Regional Hospital Center of Thiès), and who met the MAI criteria (autoimmune diseases) have been included. The data were collected on a standardised sheet and analysed by EPI INFO version 7.2. Results: A total of 121 patients were included out of 25951 records i.e a prevalence of 0.46% in internal medicine departments. In dermatology, out of 31973 patients, 95 had MAIS (systemic autoimmune diseases): 0.29% as hospital prevalence. The average age was 40.7 years in internal medicine departments compared to 37.66 years 14.8 years in the dermatology department. Patients aged 30 to 59 years represented 57.89% of the study population. The sex ratio (H/F) was 0.3 in the internal medicine departments compared to 0.17 in the dermatology department. Circumstances of discovery were incidental in 16.52% and clinical in 3.30%. Biermer disease accounted for 29.75% of organ-specific MAI. Concerning systemic presentations, rheumatoid arthritis (RA) was present in 23.14%. Lupus was more representative in dermatology (65.2%) as well as systemic scleroderma (21%), dermatomyositis (6.3%). Cytopenia was found in 105 patients, showing in detail anemia (42.9%);leukopenia (14.8%);thrombocytopenia (2.4%). Autoantibodies were tested in 58 patients (47.9%). Skin histology was contributory in all cases of systemic scleroderma and in 5 cases of lupus. The main therapy prescribed was corticosteroid therapy alone or in combination with an immunosuppressant. Conclusion: In addition of infectious diseases, Subsaharan Africa is under the era of changing face of its epidemiology, and cardiovascular diseases shows signs of emergence, like auto-immune presentations. However, the difficult apprehension of these so subtle last diseases suggests that they are few reported. Technical tools in regions should be enhanced associated to a non-binding capacity building system targeting such diseases with an emphasis on good record keeping.

Radiation-induced inflammation and autoimmune diseases

Currently,ionizing radiation(IR)plays a key role in the agricultural and medical industry,while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern.Exposure to IR has various detrimental effects on normal tissues.Although an increased risk of carcinogenesis is the best-known long-term consequence of IR,evidence has shown that other diseases,particularly diseases related to inflammation,are common disorders among irradiated people.Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people.Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR.However,the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated,and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role.Thus,cytokines,including interleukin-1(IL-1),tumor necrosis factor(TNF-α)and interferon gamma(IFN-α),play a key role in chronic oxidative damage following exposure to IR.Additionally,these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH).It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster.In the present study,we reviewed the evidence of radiation-induced diabetes and thyroid diseases,as well as the potential roles of inflammatory responses.In addition,we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.

Risk of hepatitis B virus reactivation in patients with autoimmune diseases undergoing non-tumor necrosis factor-targeted biologics

Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.

Measurement of Serum IgG4 Levels by an Established ELISA System and Its Clinical Applications in Autoimmune Diseases

Summary： IgG4-related disease （IgG4-RD） is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 eleva tion commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay （ELISA） in a variety of autoimmune diseases including systemic lupus erythematosus （SLE）, Sjogren＇s syndrome （SS）, polymyositis or dermatomy- ositis （PM/DM） and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric as-say. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23±0.16 g/L in 53 healthy controls, 0.16±0.15 g/L in 103 SLE patients, 0.22±0.18 g/L in 41 SS patients and 0.40±0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups （P〉0.05）. The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.

A PILOT TRIAL FOR SEVERE ,REFRACTORY SYSTEMIC AUTOIMMUNE DISEASE WITH STEM CELL TRANSPLANTATION

Objective To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy （HDIT） and autolognus hemopoietic stem cell transplantation （HSCT） with CD^34＋ cell selection in patients with severe, refractory autoim mune diseases. Methods Twenty-six patients with persistent systemic lupus erythematosus （SLE）, rheumatoid arthritis （RA）, primary Sjogren＇s syndrome （pSS）, or systemic sclerosis （SSc） who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease acti- vity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored. Overall treatment related mortality was 7.7% （2/26） with 1 patient died of cytomegalovirus infection and an other of severe pneumonia. Relapse occurred in 3 SLE patients （17.6%） in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index （SLEDAI） scores of SLE survivors decreased significantly （P 〈 0.01）. RA patients recorded a drop of Disease Activity Score 28 （DAS 28）. The pSS patient remained symptoms free up to now, more than 50 months aider the transplantation. Conclusion HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.

Role of myeloid-derived suppressor cells in autoimmune disease

Myeloid-derived suppressor cells(MDSCs) represent an important class of immunoregulatory cells that can be activated to suppress T cell functions. These MDSCs can inhibit T cell functions through cell surface interactions and the release of soluble mediators. MDSCs accumulate in the inflamed tissues and lymphoid organs of patients with autoimmune diseases. Much of our knowledge of MDSC function has come from studies involving cancer models, however many recent studies have helped to characterize MDSC involvement in autoimmune diseases. MDSCs are a heterogeneous group of immature myeloid cells with a number of different functions for the suppression of T cell responses. However, we have yet to fully understand their contributions to the development and regulation of autoimmune diseases. A number of studies have described beneficial functions of MDSCs during autoimmune diseases, and thus there appears to be a potential role for MDSCs in the treatment of these diseases. Nevertheless, many questions remain as to the activation, differentiation, and inhibitory functions of MDSCs. This review aims to summarize our current knowledge of MDSC subsets and suppressive functions in tissue-specific autoimmune disorders. We also describe the potential of MDSC-basedcell therapy for the treatment of autoimmune diseases and note some of hurdles facing the implementation of this therapy.

Concomitant extrahepatic autoimmune diseases do not compromise the long-term outcomes of primary biliary cholangitis

Background:Primary biliary cholangitis(PBC)patients often have concomitant extrahepatic autoimmune(EHA)diseases including Sjögren’s syndrome(SS),systemic sclerosis(SSc),rheumatoid arthritis(RA),and autoimmune thyroid disease.The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients.Methods:Medical records of PBC patients diagnosed in our institute were retrospectively reviewed.Pa-tients were followed up by a standardized telephone interview.The endpoints were defined as liver-related death and/or liver transplantation.Results:Totally 247 of the 985(25.1%)PBC patients enrolled in the study had at least one concomi-tant EHA disease.Sjögren’s syndrome(n=140,14.2%)was the most frequent one,followed by rheuma-toid arthritis(RA)(n=56,5.7%)and Hashimoto’s thyroiditis(n=45,4.6%).Patients with EHA dis-eases were more common in females(P<0.001)and in those with a family history of autoimmune disease(P=0.017).Overall,no differences were found between PBC patients with and without EHA dis-eases in terms of biochemical response rates to ursodeoxycholic acid,the incidence of hepatic events,or transplant-free survival.RA and EHA≥2 were protective factors for hepatic events in univariate Cox analysis,but the results became insignificant in multivariate analysis.Conclusions:Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.

Complexities of diagnosis and management of COVID-19 in autoimmune diseases:Potential benefits and detriments of immunosuppression

Recent advances in our understanding of coronavirus disease 2019(COVID-19)and the associated acute respiratory distress syndrome might approximate the cytokine release syndrome of severe immune-mediated disease.Importantly,this presumption provides the rationale for utilization of therapy,until recently reserved mostly for autoimmune diseases(ADs),in the management of COVID-19 hyperinflammation condition and has led to an extensive discussion for the potential benefits and detriments of immunosuppression.Our paper intends to examine the available recommendations,complexities in diagnosis and management when dealing with patients with ADs amidst the COVID-19 crisis.Mimicking a flare of an underlying AD,overlapping pathological lung patterns,probability of higher rates of false-positive antibody test,and lack of concrete data are only a part of the detrimental and specific characteristics of COVID-19 outbreak among the population with ADs.The administration of pharmaceutical therapy should not undermine the physical and psychological status of the patient with the maximum utilization of telemedicine.Researchers and clinicians should be vigilant for upcoming research for insight and perspective to fine-tune the clinical guidelines and practice and to weigh the potential benefits and detrimental effects of the applied immunomodulating therapy.

Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases:Current evidence

Dipeptidyl peptidase-4 inhibitors(DPP-4i)have an important place in the management of type 2 diabetes.The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological functions.DPP-4 regulates several immune functions,including T-cell activation,macrophage function,and secretion of cytokines.Studies have reported an increase in autoimmune diseases like bullous pemphigoid,inflammatory bowel disease,and arthritis with DPP-4i use.The relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more clearly.Whether a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious issue.Nevertheless,a heightened awareness from the clinicians is required to identify and treat any such diseases.Through this review,we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.

Engineered T cells and their therapeutic applications in autoimmune diseases

Chimeric antigen receptor T cells(CAR-T cells) are engineered recombinant T cells, which were initially used to treat hematopoietic malignancies and are now widely used in the treatment of various diseases. Considering their intrinsic targeting efficiency, CAR-T cells show considerable potential in the treatment of autoimmune diseases.Furthermore, regulatory T cells(Treg), a subset of CD4 T cells exhibiting immunosuppressive functions,have attracted increasing attention regarding CARTreg cell production. In this review, we report on recent developments in preclinical and clinical studies on CAR-T cells in autoimmune diseases and provide an outlook on opportunities and challenges of CAR-T application in such diseases.

In Vitro Biological Activity of Anti-C Ⅱ TA Hammerhead Ribozyme——A Novel Approach for Autoimmune Diseases

This study investigated the feasibility of using an hammerhead ribozyme against C Ⅱ TA, a major regulator of MHC Ⅱ antigens, to repress the expression of MHC Ⅱ molecules on Hela cells. A hammerhead ribozyme (Rz464) specific to 463-465 GUC triplet of C Ⅱ TA and its target gene were transcribed, then mixed up and incubated in vitro . The cleavage products were analyzed by PAGE and silver staining. Rz464 was then inserted into the pIRES2 EGFP vector (pRz464). Stable transfectants of Hela with pRz464 were tested for class Ⅱ MHC induction by recombinant human interferon gamma (IFN γ). mRNA of C Ⅱ TA was measured by RT PCR. Our results showed that Rz464 could exclusively cleave C Ⅱ TA RNA. When induced with IFN γ, the expression of HLA DR, DP, DQ on pRz464 + Hela was induced, and the mRNA content of C Ⅱ TA decreased too. It is concluded that Rz464 could inhibit C Ⅱ TA and thus the family of genes was regulated by C Ⅱ TA:MHC Ⅱ molecules. These results provided insight into the future application of Rz464 as a new nucleic acid drug against auto immune diseases.

PERIPHERAL BLOOD CD34^+ CELL MOBILIZATION IN 42 PATIENTS WITH SEVERE AUTOIMMUNE DISEASE

Objective To evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease. Methods Forty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2 +recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 μg·kg-1·d-1. The positive selection of CD34+ cell was performed through the CliniMACS. Results In 8.1±2.3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7±1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95×109/L and 0.035×109/L, respectively. After 2.4±0.6 times of leukapheresis, there gained 4.46×108/kg of MNC and 5.26×106/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE Disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (P<0.01). In rheumatic arthritis patients, an American College of Rheumatology criteria for 20%(ACR20) response was achieved in all five patients. Totally, 17.4% of patients whose absolute neutrophil count <0.5×109/L suffered infection, and 31.0% of patients had bone pain after the injection of rhG-CSF. Two patients suffered severe complications, one with acute renal failure and recovered by hemodialysis, the other died of thrombotic thrombocytopenic purpura. Failed mobilization occurred in three patients. Conclusions Sufficient CD34+ cells can be mobilized by low dose of cyclophosphamide and rhG-CSF. CD34+ cell mobilization for treatment of severe autoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.

Cause of Autoimmune Diseases： Anomalous Magnetic Fielads

The aim of this work is to prove the AMF （anomalous magnetic fields） from the environment cause of AID （autoimmune diseases）. The therapeutic possibilities of natural EMF （Earth＇s magnetic field） is pointed out and how to act to prevent AID is determined. Authors indicate in which magnetic fields the IS （immune system） defends the body. They also explain why, in medical literature, risk factors are mistakenly declared pathogens of AID. The magnetic fields intensity in 20 peoples＇ beds, suffering from Type 1 diabetes, was measured with proton magnetometer （accuracy of 100 nT）. The measurement results are presented on sketches, patients were transferred to the natural EMF, medical condition was monitored, and AID function IS ethiopathology was studied. The correlation between AMF and organ location where AID occurred was determined by measuring. The cells of an organism, formed in natural EMF, are in magnetic balance. When an intruder enters the body, magnetic balance disappears and leukocytes with its MF （magnetic forces） destroy intruders. In the AMF, cells get enlarged MF without magnetic balance, causing IS with its MF to attack own cells, resulting AID. When an intruder enters a tissue, tissue cells and cells of intruders gain enhanced MF. IS with its MF destroys intruders. In the literature （The China Study by T. Colin Campbell）, the food is presented as cause of number of diseases. It was found what led to such a misinterpretation. It has been proven that causes of mentioned diseases are only AMF, which can be located in any organ, and with Type 1 diabetes its spread to the whole body with strongest intensity on pancreas. AMF give tissue cells reinforced MF without magnetic balance causing IS to deplete own tissues, resulting AID. IS works perfectly without AMF and risk factors are only a consequence of AMF.