Rheumatoid arthritis

Rheumatoid arthritis is chronic autoimmune systematic inflammatory disease of connective tissue with predominant joint disease of erosive-destructive progressive polyarthritis type. The disease affects 0.5-1% of the population. About 58 million of people suffer from rheumatoid arthritis all over the world.

The exact cause of rheumatoid arthritis is unknown. The pathogenesis basis of rheumatoid arthritis consist of genetically determined autoimmune processes, which are caused by deficit of T- suppressor function of lymphocytes. The unknown etiological factor causes the immune reaction. Insult begins with inflammation of the synovium (sinovita), which then takes form of proliferative nature (pannus) with the damage of cartilage and bones. Plasmatic cells of joint oil produce changed aggregated IgG. In turn, it is recognized by the immune system as foreign antigen and plasmatic cells of joint oil, lymph nodes, spleen begin to produce antibodies to it - rheumatoid factors (RF). The most important is RF of IgM class, which appears in 70-80% of patients with rheumatoid arthritis.

Because of autoimmune inflammatory process it is formed pannus - granulation tissue that occurs from inflamed synovium, which consists of actively proliferating fibroblasts, lymphocytes, macrophages and rich with vessels. Pannus grows intensively, percolates from the synovial tissue to the cartilage and destroys it by the influence of enzymes, which are induced by production of cytokines within pannus. Gradually intrasynovial cartilage disappears, it is replaced by granulation tissue and ankylosis develops. Chronic inflammation of periarthric tissues, joint capsule, ligaments, tendons lead to deformation of joints, semiluxations, contractures. Currently there is a view, that autoimmune processes play a central role in the early stages of rheumatoid arthritis, and in later stages are more important non immune mechanisms (i.e. the ability of pannus for growth, invasion and destruction of joint cartilage).

Joint syndrome - is a leading clinical implication of rheumatoid arthritis. Typical for rheumatoid arthritis is bilateral symmetric joints decease. Start of the disease is often associated with adverse weather (spring, autumn), periods of organism physiological alteration (pubertal, postnatal, menopause). The development of rheumatoid arthritis may be caused by previous infections, cooling, trauma, stressful situation.

The most common for rheumatoid arthritis is the insult of bones, feet, wrist, knee, elbow joints. Rarely are affected shoulder, thigh joint and spine joints. Joint disease in the course of rheumatoid arthritis usually has a symmetrical character, is accompanied by a feeling of morning tightness, the sharp restriction of mobility in joints, that significantly limits the possibility of self-service (it is difficult to dress, to wash, to brash hair, to shave, etc.) and working abilities. The more active is the inflammatory process in joints, the more is the duration of the morning tightness.

Renal irritation in the form of glomerulonephritis or amyloidosis - is the most severe visceral presentation of rheumatoid arthritis. Rheumatoid glomerulonephritis usually develops at process high activity and most often is characterized by isolated urinary syndrome (proteinuria, microhematuria), which disappears after rheumatoid arthritis exacerbation reduction. Rarely, it is observed diffuse glomerulonephritis with persistent proteinuria, microhematuria, increased blood pressure, swelling, dysfunction of the kidneys. In separate cases, it is possible the outcome of glomerulonephritis into nephrosclerosis.

Kidneys lardaceous usually develops in the long course of rheumatoid arthritis (over 7-10 years) and process high activity. Main manifestations: persistent proteinuria (1-3 g / l), cylindruria, edema, arterial hypertension, gradual failure of concentrating (isohyposthenuria in the sample on Zimnitskiy) and nitro-exhale functions of the kidneys. With the development of chronic renal insufficiency anemia appears. Kidneys lardaceous may be accompanied by development of nephrotic syndrome, which is characterized with high proteinuria (protein concentration in urine makes 6-8 g / l), hypoproteinemia, hypocholesteremia, frank edemas, rapidly developing renal insufficiency, anemia.

Rheumatoid arthritis degrees of activity:

Ist degree (minimum activity). Minor pain in the joints, short morning constraint (30 minutes), minor exudative phenomena in the joints, skin temperature of the joint is normal or slightly increased. ESR is increased to 20 mm / h., the number of leukocytes in blood of normal level, level of alpha-2-globulin is increased to 12%, C-reactive protein (CRP) +, indicators of fibrinogen and several sialic acids are increased.

IInd degree (middle activity). Pain in joints not only when moving, but in quiet, constraint continues up to noon, frank pain limiting of mobility in the joints, moderate stable exudative phenomena. Skin hyperthermia over the joint is moderate. Affect of internal organs is expressed obscure, subfebrile body temperature. ESR increased - from 25 to 40 mm / h, the number of leukocytes in the blood makes 8-10 × 109 / l, content of alpha-2-globulin is increased to 15%. CRP + +, the levels of sialic acids and fibrinogen are considerably increased.

IIIrd degree (high activity). Strong pain while rest, frank exudative phenomena in the joints (significant edemas, hyperemia and increased skin temperature), tightness throughout all the day, frank mobility restrictions.

Symptoms of active inflammatory process in the internal organs (pleurisy, pericarditis, carditis, nephritis, etc.): high body temperature, ESR exceeds 40 mm / h, the number of leukocytes in the blood makes 15-20 × 109 / l, alpha globulins exceeds 15%, CRP +++, the content of fibrinogen and sialic acids is sharply increased.

Functional deterioration (FD) of locomotor apparatus:

FDI - slight limitation of movements in the joints, a feeling of tightness in the mornings, professional suitability is usually preserved, but limited a little (hard work is contraindicated).

FD II - restriction of movements in the joints, steady contractures, self-service is harden, professional suitability is usually lost.

FD III - stiffness or total lose of movement in joints, lost the ability to self-service, patient requires constant care.

RA treatment is symptomatic, aimed at reducing the degree of severity of inflammatory process in joints: glucocorticosteroids, non-steroid anti-inflammatory drugs, local anesthetic and anti-inflammatory therapy, physiotherapy.

The usage of stem cells for rheumatoid arthritis treatment is certified, at least, in 15 clinical trials. Approaches to treatment vary. One of the directions is the extraction of mesenchymal stem cells from patient’s bone marrow, their preformation into cartilage cells (chondrocytes) and injection directly into the affected joint. Another direction involves the systemic injection of hematopoietic and / or mesenchymal cells in the blood to reduce autoimmune aggression presentations.

At the Institute of Cell Therapy it is developed complex treatment methodology for rheumatoid arthritis, based on the simultaneous transplantation of hematopoietic and mesenchymal stem cells. Principal is, that in this case it is achieved three objectives: the restoration of damaged joint tissue by stimulating the patient's own regenerative resources under the influence of growth factors produced by cells, replenishment of stem reserves for regeneration of synovial, cartilage and bone tissue by mesenchymal cells, eliminating of disease autoimmune component and blocking of disease further progression due to immunosuppressive and tolerogen effects of mesenchymal and hematopoietic stem cells. The method has significant limitations: such transplantation may be used only when rheumatoid arthritis degree of activity is I-II and joints functional failure is 0-I.

Clinical example. . As an example, here you have the charts of indicators changes of the clinical duration participants of rheumatoid arthritis, which was held by the Coordinating Centre for Transplantation of organs, tissues and cells of MH of Ukraine at the Institute of Cell Therapy.

Control group (ST) – 29 29 patients, RA, activity I, functional failure of joints I, polyarthritis, seropositive, slow-progressive duration. Treatment: placvenil, delagil, methotrexat, movalis, diklofenal-sodium, indometacine, ibuprofen.

The main group (TEPC) – 21 patients, RA, activity I, functional failure of joints I, polyarthritis, seropositive, slow-progressive duration. Treatment: single transplantation of hematopoietic stem cells. Dose: 0,4 × 106/kh of body weight. Phenotype: CD34 + CD133 + CD38-CD45RAlow CD71low CD7HLA-DRlow.

• At the core group Lee functional test after 12 months in msk in 1.6 times, after 18 months - in 3.3 times better then patients of the primary group.

• Painful index of main group patients was lower: in 12 months - in 1.9 times, after 18 months - in 5.2 times.

• Inflammation index of main group patients after 12 months was lower 54%, after 18 months - 82%.
• Doctor-patient treatment estimation efficiency test (control group, major group):
  • “significant improvement” – 23/45%
  • “improvement” – 40/55%
  • “minor improvement” – 29/0%
  • “no change” – 8/0%