Newsletter Introduction Part 1
Autoimmunity (“auto” is Greek for self) is a condition where the immune system mistakenly mounts an immune response against self causing inflammation and damage. There is activation of both the humoral and cellular immune response against “self-antigens” which can be nuclear proteins e.g. snRNP, modified protein antigens like the citrullinated proteins from inflamed synovium in rheumatorid arthritis (RA) or nuclear antigens that are usually protected by nuclear membranes like antinuclear antibodies (ANA) .
An autoimmune disease can be specific, involving a single organ e.g. Crohn’s disease (intestinal tract), multiple sclerosis (brain), and diabetes mellitus Type I (insulin-producing cells of the pancreas) or general, involving multiple sites in the body e.g. systemic lupus erythematosus (SLE) and Sjorgren’s syndrome.
The causes of autoimmune disease are not clearly known and are likely multi-factorial. Some disorders are associated with genetic factors for example the association of HLA-B27 with ankylosing spondylitis. The environment can also influence the immune system to mount an inappropriate immune response and some autoimmune diseases have been associated with infectious disease triggers e.g. multiple sclerosis .
Some autoimmune diseases are associated with hormonal changes, with some occurring in pregnant women and most being more common in females. The characteristics of some of the more common autoimmune diseases are outlined in Table 1 .
|Systemic lupus erythematosus (SLE)||Different tissues||Familial or drug induced e.g. phenytoin, hydralazine. Periodic, mainly young women. Fever, chills, fatigue, weight loss, skin rashes ( “butterfly” malar rash), vasculitis, hair loss, irregular menstrual periods, lymph node enlargement, depression, psychosis and seizures.|
|Rheumatoid Arthritis (RA)||Joint synovium||Fever, loss of appetite, weight loss, joint pain evolving to specific joints (small joints of the fingers, wrists, elbows, knees, ankles), eventually joint deformities and loss of function.|
|Scleroderma (CREST Syndrome) or Progressive Systemic Sclerosis (PSS)||Connective tissue||Pain, swelling and stiffness joints, tight shiny skin, loss of appetite, weight, loss, GIT (diarrhea/constipation), kidneys, heart and lungs. Malignant hypertension causes 30% of mortality.|
|Goodpasture’s Syndrome||Lungs, kidney||Typically in young men; glomerulonephritis, haempoptysis, pallor, fatigue, haematuria.|
|Polymyositis and Dermatomyositis||Neuromuscular||Muscle weakness, shoulder or pelvis (polymyositis) skin rash on the arms, hands, face and trunk (dermatomyositis).|
|Ankylosing spondylitis||Joints, soft tissues||Progressive pain and inflammation starting in the lower back and progressing upwards.|
|Sjorgen’s Syndrome||Excocrine glands||Dry mouth and eyes.|
|Type 1 Diabetes Mellitus||Insulin producing islet cells pancreas||Fatigue, polydipsia and hyperglycaemia.|
|Grave’s disease||Thyroid||Excessive thyroid hormone, enlarged thyroid, weight loss, loss of appetite, sweating, palpitations, nervousness, heat intolerance.|
|Hashimoto’s thyroiditis||Thyroid gland||Decreased thyroid hormone, weight gain, fatigue, dry skin, hair loss.|
|Pernicious anaemia||GIT lining||Malabsorption Vit B12, anaemia, nausea, vomiting, diarrhea, constipation, blurred vision, tinnitus, peripheral neuropathy.|
|Autoimmune thrombocytopenic purpura||Platelets||Bruising and bleeding from gums, GIT, genitourinary tract and nose.|
|Vasculitis||Blood vessels||Group of disorders, variable symptoms based on which vessels affected.|
|Myasthenia gravis||Acetyl choline receptors||Severe muscle weakness initially confined to a group of muscles, progressing to global paralysis.|
Diagnosis of an autoimmune disease may be clinically difficult because symptoms may be relatively non specific unless there are obvious signs like the “butterfly” malar rash of SLE (Figure 1).
Figure 1 Typical Malar “Butterfly” Rash of SLE
A thorough family history and symptom review is necessary before initiating laboratory testing. General tests to detect inflammation like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are good initial tests followed by anti-nuclear antibodies (ANA) levels, the first screening test for the diagnosis of any autoimmune disease. After which more specific testing may be done as per the algorithm in Figure 2.
Anti-nuclear Antibodies (ANA)
Different methods to detect ANA exist including immune fluorescence, ELISA and immunoblots. Each of these methods has advantages and disadvantages. Immune fluorescent testing is considered the gold standard and is the method currently used at Lancet Laboratories. Fluorescent testing can give additional information about the type of autoimmune disease based on the fluorescent pattern in the cells (Figures 2 and 3).
Low levels of ANA antibodies may exist in 3-15% of normal individuals, titres of between 1:40 and 1:80 are considered “negative” unless there are other signs and symptoms of autoimmune disease or other elevated markers of inflammation. The prevalence of circulating ANA increases with increasing age so that about 10-37% of people over the age of 65 will have circulating ANA’s but no associated autoimmune disorder. False positive ANA tests can also occur if the patient is taking certain drugs (Table 1).
A positive ANA test is considered for any ANA titre > 1:160. Further testing and monitoring of the patient must be done for a definitive diagnosis. ANA patterns with fluorescent testing may help distinguish between some autoimmune diseases. There are 6 main types of ANA fluorescent patterns; peripheral, homogenous, cytoplasmic, nucleolar, centromere and speckled. Figure 3 shows the fluorescent microscopic appearance of 4 of these patterns. The diagnostic significance and associated diseases are indicated in autoimmune disease diagnostic algorithm (Figure 2).
Figure 2 Diagnostic Approach to Autoimmune Diseases [modified ref 2]
Figure 3 ANA IFA Patterns: in clockwise order peripheral, cytoplasmic, nucleolar, speckled. 
Other newsletters will deal with the more specific autoimmune markers outlined in Figure 2, are currently offered at Lancet Laboratories including updated diagnostic criteria for specific autoimmune diseases like Juvenile Rheumatoid Arthritis (JRA), which also causes elevated ANA levels, and Rheumatoid Arthritis (RA).
- Fundamental Immunology. Ed Paul WE. 2003. Chap 44. Systemic autoimmunity. Cohen PL. 1372-1392.
- ARUP Consult Algorithms. http://www.arupconsult.com/Algorithms/or.html
- Racanelli V, Prete M, Musaraj G, Dammacco F, Perosa F. Autoantibodies to intracellular antigens: Generation and Pathogenic Role. Autoimmunity Rev. 2011.doi 10.1016/j.autrev.2011.03.001.
- American College of Rheumatology. Antinuclear antibodies (ANA). http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ana.asp