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Diagnosis of Autoimmune Disorders

Posted By HealthcareOnTime Team Posted on 2022-06-01 Diagnosis of Autoimmune Disorders

The nation will stand along when heroic soldiers who ought to defend the boundaries are loyal but, not if they turn treasonous. In the same way one's survival is in doubt if our defense system meant to shield us, damages the cells, tissues and organs of our body. Immune system is the guardian that protects our body from foreign invaders. But when this protection system fails to distinguish between self and non-self tissues of the body they react by forming autoantibodies against tissue antigens known as autoimmunity.

Our body possess well developed mechanisms to stop autoimmune responses to tissue antigens, while any disturbances in these results in autoimmune disorders, the hallmarks of which are self-reactive T cells, autoantibodies and inflammation. Autoimmune Disorders (AID) can be classified as organ specific characterized by response against autoantigens localized to particular organ, and non-organ specific which is directed against autoantigens present throughout the body.

Development of Autoantibodies
Autoantibodies recognizes self tissue antigens, mostly intracellular enzymes and regulatory factors necessary for gene replication, repair, transcription, RNA processing and translation. The process of molecular mimicry may raise autoantibodies due to the structural similarity between the self molecules and infectious exogenous agents. As a result, antibodies and activated T cells in response to these exogenous agents react with human proteins thereby creating autoimmune response.

  • Stimuli for Autoantibody Generation
    Genetic model studies indicates two possibilities for the stimulation of autoantibodies i.e. excessive antigenic drive from antigens released from dying cells and by enhanced responses associated with intrinsic abnormalities in B or T cells. These two evidences strongly suggests that the presence of specific autoantibodies for target organs in organ-specific autoimmune diseases may be due to the inflammation.
  • Reactivity of Autoantigens
    Meffre and Wardemann suggested that 75% of immature B cells derived recombinant antibodies were polyreactive i.e. posses polyreactivity to self antigens like insulin, ssDNA and dsDNA, and are autoreactive as measured by binding capacity to HEP-2 cells. There are two checkpoints to ensure elimination of autoreactive B cells: one in the bone marrow (BM) through deletion or receptor editing, and in periphery where immature B cells become mature cells. Dysregulation of any one or both will lead to chances of autoimmune disorders.

Autoantibody Specificity

  • Dying cells and cell debris serve as antigens Neoepitomes are formed due to the enzymatic cleavage of cellular molecules during the process of apoptosis. Under normal conditions it leads to tolerance but inflammatory changes arising from UV exposure, oxidation or cleavage by granzyme B, peripheral immune system may alter the self antigens qualitatively. Anti-CCP autoantibodies is an example of autoantibody elicited by cyclic citrullinated peptides (neoepitome) in Rheumatoid Arthritis.
  • Receptor signaling defects Mutation in Btk and PTPN22 genes, encoding for B cell Receptor (BCR) signaling pathways increases the autoreactive immature B cells in blood and reduces efficiency of BCR signaling pathway. Toll-like receptor- mediated signals and BCR signals regulate autoreactive B cells entry in immature B cell pool. Any misregulation in the process will lead to the defective entry of immature B cells in blood stream.
  • Genetic abnormalities Knockout and over expression at genetic level may lead to defective antibody production.

Rheumatoid Arthritis (RA)
Globally, Rheumatoid Arthritis affects 1% of the adult population. This autoimmune disorder is characterized by inflammation which causes progressive damage of bone and cartilage that leads to loss of joint function and deformity. Its symptoms includes joint pain, swelling and stiffness. The onset of RA involves infiltration of lymphocytes, monocytes and dendritic cells in synovial cavity. Further synovial membrane or pannus expands due to proliferation of synovial tissues and activates osteoclasts which destroys bone tissue and is a major reason behind chronic inflammation in RA. The genetic and environmental factors altogether are liable to cause RA.

Risk Factors

  • Genetic factors Class II human leukocyte antigens (HLA-II) as well as non-HLA genes have been implicated in the pathogenesis of RA and its outcome.
  • Epigenetics Mutations in genes encoding epigenetic regulators result in aberrant expression and functional impairment of these factors and alter epigenetic profile. Disturbances in methylation patterns, hypermethylation, hypomethylation and cell-type specific histone methylation potentially marks the genetic risks associated with RA.
  • Age and Gender Many of the rheumatological systemic autoimmune disorder affects women more often than men; this is also true for RA. Although reasons behind disability progression are not well documented, however, X-linked factors and hormonal aspects play significant role in progression of disability, which is three times more in women than men.
  • Environmental Factors Factors like cigarette smoking, silica crystals (industrial pollutants), body microbiota disturbances, bacterial and viral infectious agents, and their components may aggravate RA pathogenesis.

Systemic Lupus Erythematosus (SLE)
It is an autoimmune disorder affecting multiple organ system of the body and is characterized by presence of anti-nuclear antibodies. SLE has a wide spectrum of severity due to the formation and deposition of autoantibodies and immune complexes leading to organ damage. It's clinical symptoms are non specific and may arise at any stage and are characterized by fatigue, fever and arthralgia, joint swelling and butterfly rash". Due to complex etiopathogenesis, patients are at high risk of morbidity and mortality, incidences of which varies by geographical location, age and gender, and are approximately 20 to 150 cases per 100,000 persons.

Owing to its non-specific signs and symptoms, presence of any four of these confirms SLE: Anti-nuclear antibody, malar and discoid rash, photosensitivity, oral ulcers, arthritis (non-erosive Jaccoud's arthropathy), serositis, renal, neurological, haematological and immunological disorders.

Autoimmune Thyroid Disorders (AITD)
AITDs can be defined as the dysregulation of T cell mediated immune system resulting in lymphocytic infiltration in thyroid gland. Failure of immune tolerance in these disorders results in organ-specific reactivity of autoantibodies against self-thyroid antigens. Interaction between genetic, environmental and endogenous factors can result in dysregulation of the immune system owing to the autoimmune response. Following genetic and environmental factors have been identified so far

  • Genetics factors HLA-DR gene locus and Non-MHC genes (CTLA-4, CD40, PTPN 22, thyroglobulin, and TSH receptor genes)
  • Environmental factors lodine deficiency, medications, infection, smoking and stress.

Thyroid disorders are broadly classified into two types

  • Graves disease (GD) It is an inherited autoimmune disorder, in which autoantibody mimic TSH and activate TSH receptor causing hyperthyroidism. Common symptoms of GD includes thyroid enlargement, goiter and excessive action of thyroid hormone which may be present individually or together.
  • Hashimoto's thyroiditis (HT) In this disorder, intrathyroidal lymphocytic infiltration leads to hypothyroidism due to gradual damage to thyroid gland. Individuals with HT may or may not have goiter as a symptom but presence of anti TPO and TG antibodies is prevalent in their serum.

With the advancement in the stage of the disease, HT and GD can change from one form to another. The prevalence of AITD is about 5%, with women aged between 30 to 50 at high risk of disease.

Diagnosis of Autoimmune Disorders
The clinical detection of autoimmune disorders is an important measure because effective treatment starts only after its diagnosis and in most of the cases early treatment may help in minimizing severity to much extent. Various testing methods can serve as a hallmark for prognosis and severity of the disorder. Some of them are described below.

ANA Testing
Antinuclear antibodies test, also known as ANA Test, is an excellent diagnostic test for disorders associated with autoimmunity, which includes active and inactive SLE, mixed connective tissue diseases (MCTDs), scleroderma, Sjogren's syndrome, primary biliary cirrhosis (PBC) and polymyositis. ANA test is used to determine the presence of autoantibodies against self antigens representing cellular components such as ch as chromatin, histone, nucleic acid, nuclear and ribonuclear protein, where clinically important target complexes of antigens are of RNA-protein or DNAprotein.

Testing Methods

  • ELISA Enzyme-linked Immunosorbent Assay or ELISA is used to detect the presence of autoantibodies for the diagnosis of autoimmune disorders. In this techniques, patient's sera is incubated in multi-well plate coated with homogenized antigens. The anti-human antibody linked with enzyme tag is then introduced in multi-well plate followed by substrate. The change in color helps to quantify the results by colorimetry. Advantages of this technique is simplicity of procedure and speed.
  • Immunofluorescence Assay It is a traditional method which is also used for analysis of ANAs. It has complex assay procedures, tedious and require expertise handling.
  • ANA Blot It is a membrane based enzyme immunoassay for qulitative detection of autoantibodies against known antigen.

Human Leukocyte Antigen (HLA) Determination
Techniques like gel electrophoresis, PCR and ELISA can be used to detect Human Leukocyte Antigen (HLA) or Major Histocompatibility Complex (MHC) for diagnosis of Autoimmune Disorders. MHC was first found to be associated with Hodgkin's lymphoma in which HLA-B antigen was found in high frequency. Studies show the link between MHC class Il genes and Autoimmune Disorders like RA and graves' disease. MHC genes encodes for molecules that are responsible for exogenous antigen presentation to CD4' Th cells which indicates its role in development of Autoimmune Disorders. Early diagnosis and treatment ensures the minimum severity and can eliminate the worse outcomes. Therefore, it is essential to consult the experts when early symptoms are visible. Although, core reason of autoimmunity in Autoimmune Disorders is not evident, its management helps to eliminate the development and painful symptoms to much extent.

Current approaches for treatment of Autoimmune Disorders uses immunosuppressors to restore non-aggressive immune system. These immunosuppressive therapies are helpful and promises positive results for patients diagnosed with poor prognosis. They are recommended to control overactive immune system and reduce severity of the disease. Although not long lasting, but they help to reduce the symptoms to much extent. Major complication faced is remission of disease which may be delayed by continuous vigilance. Hemopoietic stem cell transplantation (HSCT) is also a curative option in treating Autoimmune Disorders such as sclerosis, lupus, etc.


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