Markers of autoimmune connective tissue diseases (CTDs)

Causes and development of autoimmune diseases

The causes of autoimmune connective tissue diseases include:

1. Infection with a microorganism, antigenic determinants (epitopes) of the most important proteins which resemble antigenic determinants of normal tissues of the host organism. According to this mechanism, developed autoimmune glomerulonephritis after streptococcal infection or autoimmune reactive arthritis after gonorrhoea.
2. Destruction or necrosis of tissues or changes in their antigenic structure, so the changed tissue becomes immunogenic for the host organism. According to this mechanism, developed autoimmune chronic active hepatitis after suffering hepatitis B.
3. Impaired integrity of tissue barriers, separating some of the organs and tissues from the blood and therefore immune from the aggression of lymphocytes of the host. However, because normal tissues these antigens in the blood are not, the thymus does not produce the destruction of autoaggressive lymphocytes against these tissues. According to this mechanism, developed autoimmune thyroiditis.
4. Hyperimmune condition (pathologically enhanced immune system) or immunological imbalance with the impaired "selector" function of the thymus, which suppress autoimmunity, or decreased activity of T-suppressor subpopulation of cells.

The mechanism of development of many autoimmune diseases (systemic scleroderma, periarteritis nodosa, acquired hemolytic anemia, etc.) is not clear. Most of them develops the type of allergic reaction of delayed type with involvement of immune lymphocytes. In autoimmune lesions of blood is paramount in the blood of circulating antibodies.

As autoantigens can join proteins, nucleic acids, phospholipids, sugar, immunoglobulins (rheumatoid factor — autoantibodies to IgG).

In the blood in norm in a small number of natural autoantibodies, usually of IgM class do not cause pathological processes, and stimulate tissue regeneration.

Autoimmune diseases can be divided into:

1. Organ-specific (with a lesion of the thyroid gland, adrenal glands, stomach, pancreas — Hashimoto's thyroiditis, primary myxedema, thyrotoxicosis, pernicious anemia, Addison's disease, diabetes type I etc.).
2. Organospecificity (with involvement of skin, kidney, joints, muscles — dermatomyositis, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, etc.).

Detection in serum of various autoantibodies is sometimes key diagnostic value for confirmation of a disease, is closely associated with disease activity or may determine the prognosis. Applicable laboratory tests are an important tool when considering treatment options and monitoring the effectiveness of the therapy.

Of prognostic importance is the change of the level of antibodies (titers increase and decrease). Most autoantibodies are not specific for any disease, they are found in various combinations.

 

Rheumatic diseases

Rheumatic (autoimmune) connective tissue diseases include:

• systemic lupus erythematosus (SLE)
• systemic scleroderma
• Sjogren's syndrome
• mixed connective tissue disease
• polymyositis or dermatomyositis
• rheumatoid arthritis (RA)
• myasthenia gravis
• multiple sclerosis
• sometimes antiphospholipid syndrome and periarteritis nodosa, although most recent publications in these disease "opens" a group of systemic vasculitis

 

Laboratory tests of rheumatic diseases

Laboratory tests of rheumatic diseases includes the identification of:

• autoantibodies
• immunoglobulins
• circulating immune complexes
• components of the complement system
• proteins of acute phase of inflammation
• indicators of endothelial dysfunction and damage
• genetic markers
• markers of bone metabolism

 

Rheumatoid factor (RF)

Rheumatoid factor (RF) is an antibody against the Fc-fragment of IgG. Most often these antibodies are IgM, but sometimes IgG-, IgA-, IgE-antibodies.

Rheumatoid factor (RF) have 75-80% of patients with rheumatoid arthritis, it also find in Sjögren's syndrome, scleroderma, dermatomyositis, hyperglobulinemia, b-cell lymphoproliferative diseases.

The presence of rheumatoid factor is considered an important prognostic sign of rapidly destructive lesions of joints and systemic manifestations in rheumatoid arthritis (RA).

 

Antibodies to cyclic citrullinated peptide (anti-CCP)

Antibodies to cyclic citrullinated peptide (anti-CCP) are a heterogeneous group of autoantibodies that recognize the antigenic determinants of filaggrin and other proteins containing atypical amino acid citrulline. These antibodies are present in 79% of sera from patients with rheumatoid arthritis (RA).

Antibodies to cyclic citrullinated peptide (anti-CCP) are detected at a very early stage of rheumatoid arthritis (RA). In addition, the test allows to differentiate between erosive (anti-CCP-positive patients) and non-erosive (anti-CCP-negative patients) forms of rheumatoid arthritis (RA).

 

Antibodies to modified citrullinaemia vimentine (anti-MCV)

Vimentin is a protein of the cytoskeleton of different cell types such as cells of the mesenchyme and endothelium, fibroblasts, chondrocytes and osteocytes. It is used as a marker of soft tissue tumors.

Vimentin synthesized and modified by macrophages under the regulation of proinflammatory and anti-inflammatory cytokines and is found in synovial fluid of patients with rheumatoid arthritis (RA). About half of the RF-negative patients detected by anti-MCV.

 

Circulating immune complexes (CIC)

The formation of circulating immune complexes (CIC) is a physiological defense mechanism, leading to fast elimination via the reticuloendothelial system either endogenous or exogenous antigens (microorganisms, viruses, parasites, plant antigens, antigens of fungi, pollen or food).

High levels of circulating immune complexes (CIC) and ecological feasibility study in serum and/or in other biological fluids is observed in many inflammatory and malignant diseases that may cause the development of pathology.

Determination of circulating immune complexes (CIC) and ecological feasibility study in serum is an important marker to assess disease activity, especially in autoimmune diseases.

 

The frequency of finding antibodies (%) in autoimmune diseases

Disease	anti-dsDNA	anti-osDNA	anti-histone	anti-SS-A (Ro)	anti-SS-B (LA)
Systemic lupus erythematosus (SLE)	>90	>90	30-50	10-30	30-50
Medicinal lupus erythematosus (MLE)	-	30-50	50-90	-	-
Sharp's syndrome / mixed connective tissue disease	10-30	10-30	-	-	-
Rheumatoid arthritis (RA)	-	30-50	30-50	10-30	-
Sjogren's syndrome	10-30	10-30	-	>90	>90
Scleroderma	10-30	10-30	-	10-30	-
Photosensitive dermatitis, dermatomyositis	10-30	10-30	-	-	-

 

Disease	anti-Sm	anti-RNP/Sm	anti-Scl-70	anti-Jo-1
Systemic lupus erythematosus (SLE)	10-30	10-30	-	-
Medicinal lupus erythematosus (MLE)	-	-	-	-
Sharp's syndrome / mixed connective tissue disease	-	>90	-	-
Rheumatoid arthritis (RA)	-	-	-	-
Sjogren's syndrome	-	-	-	-
Scleroderma	-	-	>90	-
Photosensitive dermatitis, dermatomyositis	-	-	-	50-90