SLE - systemic lupus erythematous

Question 1

Definiton of SLE

Answer 1

a asystemic autoimmune rheumatic disease

Question 2

characterized by what? (5)

Answer 2

• chornic inflammation
• immune response driven by self antigen
• affects multple organs systems
• episodic in nature with flares and remission
  -highly variable in sevrity

Question 3

Examples of what it can affect?

Answer 3

skin, joints, kidneys, blood cell lines, serosal surfaces and brain

Question 4

Epidmiology - women or men? race? age?

Answer 4

1 in 200 canadains, women (10 times more prone), b/w 15-44, african, asian and indigenous people

loweste prevalence in white men

Question 5

A complex disease with causes such as:

Answer 5

1. interactions between inherited and poorly defined environmental factors
2. genetic defects in the complemnt pathway, rare but strongest risk factor
3. mutations in TREX 1 on the X chromosome (Klinefelter syndrome)
4. Environmental factors

Question 6

what are some environmental fctors?

Answer 6

grugs, viral infections, UV light, tobacco, alchol, crystalline silica

Question 7

Pathogenisis: diagram

Answer 7

autoantigens become clustered in apoptotic cells and it is here that they are modified

Question 8

What causes SLE?

Answer 8

inability to properly clear away apoptotic cells by macrophages, so material in cell is left behind, this material causes auto immunity and immune repsonse is moounted

Question 9

what happenes when an immune reponse is mounted?

Answer 9

In the lymph node T cells are then relased - t helper 1 and T helper 2

T helper 2 deals with the humoral antigen reposne (what we are concerned with)

TH2 promote B cell actiavtion

B cells can also be activated via IL-6, IL-10, BLS and BAFF

These then go to the plasma cells where In conjunction with TNF immune complexes are formed and autoimmunity takes place

It also forms B memory cells

Question 10

Role of IL-6, Il-10, BAFF, BLYS

Answer 10

activate B cells

BAFF- b lymphocte activoing factor

BLYS - B lymphocyte stimulator

Question 11

MEc thru whihc SLE casues tissue injury

Answer 11

1. immune complexes to ligate the Fcγ receptor, which activates myelomonocytic cell effector functions. The deposition of immune complexes in the kidneys, joints, and skin underlies several of the central clinical features of SLE.
2. Autoantibodies bind to extracellular molecules in the target organs and activate inflammatory effector functions at that site, with consequent tissue damage. Examples of this phenomenon include autoimmune hemolytic anemia and antibody-mediated thrombocytopenia, as well as the photosensitive skin disease of neonatal lupus syndrome
3. Autoantibodies directly induce cell death by ligating cell surface molecules or by penetrating into living cells and exerting functional effects.

Question 12

what is to know about type 1 interferon

Answer 12

it amplifies pathways in SLE

Question 13

In simple terms describe how SLE happnes

Answer 13

1. predisposing factors
2. abnormal immune response _ mount B and T cells forming:
3. autoantibodies immune complexes
4. casuing inflammation
5. damage

Question 14

Propagation of tissue injury simplified

Answer 14

1. generation adn depotioon of immune complexes - ligating of Fcgamma - activation of myelomonocytes
2. binding to extracellualr molecules ( photsensitive skin disease of neonatasl lupus syndrom)
3. autoantiboides penetrating livign cells and generating more antigen - auto -amplication (type 1 interferon)

Question 15

Clinical presentation

Answer 15

women of childbearing age
flares
symptoms variable
specific autoantibodies in=s universal
several organ systems affected
neonatal SLE syndrome

S and S - fever, prostration, weight loss, anemia

Question 16

what is libman sacks

Answer 16

myocarditis

Question 17

if active what can we expect to see elevations in?

Answer 17

serum aspartate aminotransferase, and alanine aminotransferase (AST and ALT)

Question 18

What is Sicca symdorm

Answer 18

dry eyes or mouth

Question 19

What test can we use to diagnose SLE?

Answer 19

ANA test - if positive > 95% of patients have SLE

Question 20

organ involvement

Answer 20

SLE can affect various organ systems, including musculoskeletal, cutaneous, renal, neurological, cardiovascular, hematological, gastrointestinal, and ocular systems.

Question 21

Klinefelter syndrome

Answer 21

Mutations on TREX 1 on x chromosome