Immune system (immune system) abnormalities generally occur in three situations: immunodeficiency syndromes, allergies and autoimmune diseases. In fact, associations between immunodeficiency syndromes and autoimmune diseases (eg, selective IgA deficiency or autoimmune diseases with frequently variable immunodeficiency tables) have been known for a long time. However, information that allergic diseases and autoimmune diseases may be related has recently attracted attention.
Allergy can basically be defined as an abnormal and exaggerated immune response to harmless proteins (antigen/antigens) of external origin. Autoimmunity results from abnormal responses to endogenous antigen(s). However; It is not possible to draw a clear boundary between allergic diseases and autoimmune diseases. For example; both rheumatoid arthritis and allergic encephalomyelitis can be experimentally induced by exogenous antigens; In addition, during chronic allergic diseases, sensitization to autoantigens (internal origin, that is, to the person’s own antigens) can be observed over time and the autoimmune component can be added to the original state.
Both allergies and autoimmune diseases can be classified as hypersensitivity (hypersensitivity) or immunopathological (immunological abnormal) conditions. As a result, in both cases, there is an excessive immune response, starting with any internal or external antigen, followed by tissue or organ damage.
Both conditions are caused by congenital genetic effects and added environmental factors (infections, drugs, chemicals, foods, UV radiation, etc.). Perhaps the only natural difference between the two that could be significant; In autoimmune diseases, the antigen cannot be eliminated and the disease persists in a chronic state. However, in allergic diseases, although the original antigen is avoided, the disease may become chronic (such as chronic bronchial asthma, chronic atopic dermatitis and chronic urticaria).
Th1/Th2 immune response hypotheses are used to understand the mechanisms of many diseases. It is known that there is a reciprocal and inverse relationship between the two immune responses. For example; It is known that in a person with a Th2 immune response-related disease, another Th1 immune response-related disease is rarer. There are some studies showing that some atopic (allergic) diseases are less common in patients with autoimmune diseases and support this hypothesis (1,2). Contrary to these findings, there are also studies showing that in some cases, both diseases go hand in hand (3). In addition; An increased incidence of autoantibodies (anti-TPO) to the thyroid peroxidase enzyme (4) and the presence of high levels of anticardiolipin antibodies (ACA) (5) have been observed in certain allergic disease states in children.
Therefore, allergies and autoimmunities can be seen both in parallel and at the same time, but there are also some differences.
In this article, I will talk about the similarities, differences and relationships between allergic diseases and autoimmune diseases.
Factors that play a role in the development of allergic or autoimmune disease:
In both cases, mechanisms in which genetic and environmental factors are effective together are responsible.
Intrinsic factors:
The main factors affecting the emergence of immunopathological diseases are HLA (tissue type) genes, genes encoding cytokines (small proteins that carry news between cell and cell) and hormonal factors. However; Clearly, there is not enough data to show that both allergic and autoimmune diseases occur together on a certain genetic basis.
Genetic effects:
The role of genetic factors in allergic and autoimmune diseases has been demonstrated by the higher frequency of these diseases (25-80%) in identical twins. In addition, the risk of allergic disease is increased in children whose parents have atopic disease. If both parents have an allergic disease, the risk in the child goes up to 75%.
Human genome studies have shown that there are many genes in all chromosomes related to the source of various diseases (6). Certain genes are characteristic for certain diseases (eg HLA B27 for ankylosing spondylitis; ADAM33 for asthma).
HLA System
Specific immune response begins with the presentation of the body’s own or foreign antigen to T lymphocytes with HLA molecules. HLA genes make up the most variable part of the human genome. In previous studies, the frequency of individual gene variability in autoimmune and allergic diseases has been extensively studied. Some HLA-related diseases are allele-only (as in ankylosing spondylitis and HLAB27); whereas others are associated with polymorphism of many gene alleles of HLA class 1 and 2 (as in Type 1 DM and MS) (6). In addition, some alleles pose a risk in the onset of the immunopathological response, while some alleles are protective (7). On the other hand, while the same allele poses a risk for one disease, it has been shown to be protective for other diseases. For example; HLADR B1-07 is associated with allergic rhinitis (8), asthma (9) and atopic eczema (10). Again, the same allele plays an important role in the emergence of mite allergy and in the development of bee allergy, while preventing the development of autoimmune diseases such as Basedow Graves and immune thrombocytopenia (11,12).
Genes Encoding Cytokines and Their Receptors
Cytokines play a key role in regulating both a physiological and a pathological immune reaction. The genes for cytokines and their receptors are distributed throughout the genomic structure. Functional variability of cytokine genes can result in underproduction, underproduction, or overproduction of a particular cytokine. In this case, changes occur in the Th1/Th2 balance. It has been claimed in many studies that there are associations between cytokine gene variability and Th1/Th2 mediated diseases. However, despite this; It is also well known that the Th1/Th2 paradigm is not responsible for the pathogenesis of all autoimmune and allergic diseases (7). Recently, regulatory T (Treg = regulatory T) lymphocytes and Th17 cells have also been identified; These cells also play different roles in the development of autoimmune and allergic diseases.
Variations in the genes of cytokines and their receptors appear to be critical genetic factors for the development of abnormal immune reactions; It is associated with the frequency of allergic and autoimmune diseases.
External (External) Factors:
Allergic manifestations result from an immunopathological reaction triggered by a particular allergen. Clinical symptoms usually disappear after complete avoidance or cessation of exposure to the allergen. However, it is not possible to avoid some allergens; this is why some atopic diseases are chronic. On the other hand, people with a genetic predisposition to atopy may develop multiple allergies. External factors other than the allergen can also lead to the rapid development of sensitivity to certain antigens (eg, with increased entry of allergens into the body as a result of infectious diseases and destruction of mucous membranes by toxic agents).
In autoimmune diseases and allergies, infection plays a role in two different ways: both as a trigger and as a protective factor. The “hygiene theory”, which emerged as a result of many epidemiological and experimental studies in allergic diseases, can be given as an example here. On the other hand, the occurrence of an infection or inflammation in allergic diseases may lead to allergic symptoms or worsen existing findings.
Infections are one of the most important external factors as a triggering mechanism in autoimmune diseases. Thus, infections can lead to the formation of an autoimmune disease. Clinical signs of autoimmune disease may appear after a while after infectious diseases. In addition, as with allergies, some infections may be protective against the development of autoimmune diseases, according to hygiene theory.
Drugs, chemicals, UV rays can increase the frequency of autoimmune diseases. This may be due to modification (replacement) of intrinsic antigens and destruction of regulatory mechanisms. In the same way, hypersensitivity to drugs or some chemicals may cause allergy symptoms. In addition to all these; Although rare, autoimmune diseases can also occur during allergy treatment. For example: Sjögren’s syndrome development has been reported after allergen-specific immunotherapy (13).
COMMON MECHANISMS OF TISSUE DESTRUCTION IN AUTOIMMUNE AND ALLERGIC DISEASES
Type 1 Immunopathological Reaction:
The basis of most allergic diseases is type 1 immunological abnormal reaction in Coombs and Gel’ classification. In this type of reaction, antibodies called IgE are produced against allergens; As a result of the combination of this antibody with the allergen on some cell surfaces, the reaction begins with the secretion of harmful enzymes and proteins. Although this type of immune response may lead to tissue destruction, such a response has only been demonstrated in experimental animals in autoimmune diseases (14). In addition, some studies have shown that there is an increase in IgE in autoimmune diseases (15)
Type 2 Immunopathological Reaction:
It is a condition that occurs through IgG and IgM type antibodies. IgM antibodies activate the complement, leading to antibody-mediated cellular toxicity (ADCC). Drug allergies and many autoimmune diseases develop due to such reactions.
Type 3 Immunopathological Reaction:
It occurs through immune complexes formed as a result of antibody-antigen combination. The immune complexes formed cannot be removed by phagocytes and are stored in tissues such as the vessel wall, kidneys, glomeruli, and joint synovium. Immune complexes bind to the Fc receptors of phagocytes or trigger complement to cause a reaction. This results in inflammation (such as SLE, RA, PAN, glomerulopathies, serum sickness, allergic alveolitis).
Type 4 Immunopathological Reaction:
It is called delayed type hypersensitivity reaction. It develops 48 hours after exposure to the antigen. It is formed by Th1 lymphocyte, monocytes and macrophage systems. Granuloma formation occurs as in sarcoidosis and mycobacterial infections (such as Tuberculosis). Allergic contact dermatitis, Type 1 Diabetes, multiple sclerosis occur as a result of such immune reactions.
TREATMENT APPLICATIONS IN ALLERGIC AND AUTOIMMUNE DISEASES
The gold standard in allergic diseases is to avoid allergens. However, this is not possible in autoimmune diseases except Celiac. Because antigens are intrinsic proteins. However, in general terms, the treatment used in both allergic diseases and autoimmune diseases are biological agents containing monoclonal antibodies as well as corticosteroids (cortisone) and immunosuppression (immune system suppression).
However; Basic treatment strategies may be different in allergic and autoimmune diseases. In allergic diseases; if possible, allergen avoidance and allergen immunotherapy (allergy vaccination) are the main treatments. In addition, immunosuppressive (immunosuppressive) drugs can be used in mild and severe types of allergic diseases. In autoimmune diseases, corticosteroids and immunosuppressives are the first choice in treatment. Autoantigen immunotherapy is among other possible treatment strategies.
CONCLUSION
1. Allergic diseases occur as a result of an excessive immune response to an external antigen (allergen). Autoimmune diseases, on the other hand, generally occur against an internal antigen. It can also occur with external application of the antigen in autoimmune disease.
2. Many abnormalities in the regulation of the immune system may be effective in the formation of both pathological conditions.
3. Both immunopathologies may have similar clinical findings and differential diagnosis may be difficult. Allergy can mimic autoimmune disease.
4. Both allergic disease and autoimmunity can occur in the same patient.
5. Similar treatments can be used in both pathological conditions.
References:
1- Meerwaldt R, Odink RJ, Landaeta R, Aarts F, Brunekreef B, Gerritsen J, et al. A lower prevalence of atopy symptoms in children with type 1 diabetes mellitus. Clin Exp Allergy 2002;32:254-5.
2- Hartung AD, Bohnert A, Hackstein H, Ohly A, Schmidt KL, Bein G. Th2-mediated atopic disease protection in Th1-mediated rheumatoid arthritis. Clin Exp Rheumatol 2003;21:481-4.
3- Edwards LJ,Constantinescu CS. Aprospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic. Mult Scler 2004;10:575-81.
4- Lindberg B, Ericsson UB, Fredriksson B, Nilsson P, Olsson CM, Svenonius E, et al. The coexistence of thyroid autoimmunity in children and adolescents with various allergic diseases. Acta Paediatr 1998;87:371-4.
5- Ricci G, Maldini MC, Patrizi A, Pagliara L, Bellini F, Masi M. Anticardiolipin antibodies in children with atopic dermatitis. J Autoimmune 2005;24:221-5.
6- Shiina T, Inoko H, Kulski JK. An update of the HLA genomic region, locus information and disease associations: 2004. Tissue Antigens 2004;64: 631-49.
7- Bart??ková JŠA, Kayserová J. Alergie a autoimunita-jin a jang imunopathologie. Alergie 2006;2:107-16.
8- Yang L, Zhang Q, Zhang P. Analysis of HLA-DRB1 allele polymorphism for patients with allergic rhinitis. Zhonghua Er Bi Yan Hou Ke Za Zhi 1999;34:147-9.
9- Moffatt MF, James A, Ryan G, Musk AW, Cookson WO. Extended tumor necrosis factor/HLA-DR haplotypes and asthma in an Australian population sample. Thorax 1999;54:757-61.
10- Saeki H, Kuwata S, Nakagawa H, Etoh T, Yanagisawa M, Miyamoto M, et al. HLA and atopic dermatitis with high serum IgE levels. J Allergy Clin Immunol 1994;94:575-83.
11- Inaba H, MartinW, De Groot AS, Qin S, De Groot LJ. Thyrotropin receptor epitopes and their relation to histocompatibility leukocyte antigen-DR molecules in Graves’ disease. J Clin Endocrinol Metab 2006;91:2286-94.
12- El Neanaey WA, Barakat SS, Ahmed MA, Al Nabie WM, Ahmed ME. The relation between HLA-DRB1 alleles and the outcome of therapy in children with idiopathic thrombocytopenic purpura. Egypt J Immunol 2005;12:29-38.
13- Turkcapar N, Kinikli G, Sak SD, Duman M. Specific immunotherapy induced Sjogren’s syndrome. Rheumatol Int 2005;26:182-4.
14- Charles N, Hardwick D, Daugas E, Illei GG, Rivera J. Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat Med. 2010;16:701-7.
15- Rebhun J, Quismorio F Jr, Dubois E, Heiner DC. Systemic lupus erythematosus activity and IgE. Ann Allergy. 1983;50:34-6.
Wishing you healthy days…
Prof. Dr. Cengiz KIRMAZ
