Genetics, rheum, asthma and transplantation

Question 1

Mechanism of asthma?

Answer 1

Allergen interacts with IgE molecule on the mast cell, which lead the mast cell to degranulate and release Histamine. Histamine cause the muscles to contract and attract other cells (T- and B-lymphocytes). This muscle contraction decreases the FEV1

Question 2

What is Scleroderma?

Answer 2

Autoimmune disease characterized by fibrosis of the skin, blood vessels and other organs (lungs, GI tract, kidneys)

Question 3

Diagnosis of asthma? (3)

Answer 3

Asthma: reversible obstructive airway disease
Diagnosis:
- Increase of 12% change in FEV1 after inhaled bronchodilator
- Decrease of 20% change in FEV1 after inhalation of methacholine or histamine
- Decrease of 15% following standardized exercise challenge

Question 4

Prevention of GVHD following blood transfusion?

Answer 4

Irradiation of fresh blood products to inactivate T lymphocytes

Question 5

What are the symptoms of Sclorederma? (2)

Answer 5

 CREST syndrome

 Raynaud’s phenomenon

Question 6

What is DiGeorge Syndrome?

Answer 6

Deletion 22q11, in the region of gene 6 (use FISH or microarray!)/microdeletion in chromosome 22

Question 7

Treatment of Familial Mediterranean Fever?

Answer 7

Colchicine: prevents inflammatory attacks and the deposition of amyloid by interfering with tubulin/microtubules. This reduces the number of WBC traveling to inflamed areas

Question 8

What occurs with graft vs host disease?

Answer 8

• Graft attacks the host (GVHD): Donor T-lymphocytes attack host following interaction with human leukocyte antigens (HLA) expressing peptides: HLA I, and HLA II (encoded by MHC)

Question 9

MHC class II matching is essential for what transplants?

Answer 9

Bone marrow transplant

Question 10

Clinical manifestations of GVHD following blood transfusion? (5)

Answer 10

	Skin rash
	Fever
	Diarrhea, gut dysfunction
	Pancytopenia (bone marrow aplasia)
	Hepatitis

Question 11

Mechanism of GVHD following solid organ transplant?

Answer 11

Immune-mediated or large number of immune competent cells in the graft are transplanted into the pharmacologically immunosuppressed recipient

Question 12

What are the treatments for asthma? (3)

Answer 12

• Anti-inflammatory: steroids
• Anti-mediators: antihistamines, antileukotrienes (you must target both IL-4 and IL-13)
• Anti-IgE: Omalizumab

Question 13

Why is bone marrow not affected in GVHD following an allogeneic stem cell transplant?

Answer 13

 Bone marrow is not affected; no pancytopenia. This is because there’s no recipient bone marrow cells, so the graft cells are the only cells there

Question 14

What is Systemic Lupus Erythematosus?

Answer 14

Systemic autoimmune disease characterized by immune complex deposition in the affected organs

Question 15

Mechanism of GVHD following blood transfusion?

Answer 15

Rare attack on recipient tissues by T lymphocytes in the transfused product

Question 16

Treatment for GVHD following solid organ transplant?

Answer 16

Systemic steroids

Question 17

Criteria for diagnosis for Systemic Lupus Erythematosus?

Answer 17

Criteria are not for diagnosis! Only for studies! Diagnosis is based on expert opinion

Question 18

MHC class I matching is essential for what transplants?

Answer 18

Solid organs (especially kidneys)

Question 19

Risk factors of GVHD following an allogeneic stem cell transplant? (6)

Answer 19

	Matched unrelated donor
	Mismatched related donor
	Mismatched unrelated donor
	Mobilized blood cell graft
	Total body irradiation
	Patient and donor age

Question 20

Mechanism of Familial Mediterranean Fever?

Answer 20

Familial Mediterranean Fever: hereditary inflammatory disorder due to mutation in MEFV gene (16p13.3)
MEFV codes for Pyrin, which is responsible for deactivation of inflammation during immune response. Mild infection will thus trigger intense immune response and inflammation

Question 21

What is Sjogren’s Syndrome?

Answer 21

Sjogren’s Syndrome: autoimmune disease affecting the exocrine glands (no saliva)

Question 22

Types of cutaneous manifestations of Systemic Lupus Erythematosus? (3)

Answer 22

• Malar Rash: butterfly distribution of non-scaring rashes around the nose
• Subacute cutaneous lupus erythematosus: non-scaring, photosensitive either of annular form or papulosquamous
• Discoid rash: scarring and depigmentation rash that affect the dermis

Question 23

What is Mixed connective tissue disease?

Answer 23

Manifestations similar to all other connective tissue diseases (Systemic lupus erythematosus, Scleroderma, Sjogren’s syndrome, Inflammatory arthropathies, Inflammatory myositis, Systemic vasculitis)

Question 24

Test for inflammatory markers? (2)

Answer 24

• Erythrocyte sedimentation rate

- C-reactive protein

Question 25

What are the Billigham's crieteria for GVHD? (3)

Answer 25

- Graft must contain immunologically competent donor cells o Donor T-lymphocytes attack host following interaction with human leukocyte antigens (HLA) expressing peptides: HLA I, and HLA II (encoded by MHC) - Host must be unable to reject/eliminate the donor cells of the graft o Host must be immunosuppressed, so it can’t stop the immune attack or host must be genetically similar to the donor so that it can’t recognize the donor as ‘non-self’, and so doing, can’t reject the donor cells - Host and graft must antigenically different from each other o Host must express tissue antigens that are nor present in the donor and thus can be recognized as foreign (these differences occur at the level of histocompatibility antigens)

Question 26

Specific clues indicating autoimmune diseases? (6)

Answer 26

- Arthritis - Skin rashes - Mucosal ulcers - Ocular symptoms - Lung involvement - Renal dysfunction

Question 27

Symptoms of Familial Mediterranean Fever? (6)

Answer 27

Symptoms (during an attack): - Recurrent fever - Peritonitis - Pleurisy - Painful, swollen joints - Characteristic ankle rash - Possible amyloidosis, which can lead to renal failure

Question 28

What are the symptoms of Sjogren's Syndrome? (3)

Answer 28

 Xerostomia (dry mouth)  Xerophthalmia (dry eyes)  Produce anti-RO (SSa) and anti-La (SSb) autoantibodies

Question 29

Occurrence of Familial Mediterranean Fever?

Answer 29

Autosomal recessive

Question 30

Risk factors of GVHD following solid organ transplant? (2)

Answer 30

 HLA-mismatch between donor and recipient |  Age

Question 31

What is the role of IL-4 and IL-13 in asthma?

Answer 31

IL-4 and IL-13 are essential to asthma pathophysiology since they participate in the making of IgE

Question 32

Occurence of DiGeorge Syndrome?

Answer 32

Autosomal dominant

Question 33

Population of Systemic Lupus Erythematosus?

Answer 33

Population: mostly women of child-bearing age (16-55yrs)

Question 34

Risk factors of GVHD following blood transfusion? (8)

Answer 34

```  Immune suppressed • Stem cell transplant recipients • Congenital T cell deficiencies • Aplastic anemia deficiencies • Chemo patients  Premature neonates  Granulocyte transfusion recipients  Some hematologic malignancies (Hodgkin lymphoma)  Receiving blood from a relative, homozygous donor ```

Question 35

Types of autoimmune rheumatic diseases? (7)

Answer 35

- Inflammatory arthropathies - Inflammatory myositis - Systemic vasculitis - Systemic Lupus Erythematosus - Scleroderma - Sjogren's Syndrome - Mixed Connective tissue disease

Question 36

Dysmorphic features of DiGeorge Syndrome? (4)

Answer 36

- Telecanthus - Puffy eyelids - Wide nasal bridge - Small mouth

Question 37

Treatment for GVHD following an allogeneic stem cell transplant?

Answer 37

 For chronic GVHD: systemic steroids with local care

Question 38

What is a rheumatic disease?

Answer 38

Rheumatic disease: a disease resulting from a disordered immune reaction in which there is an antibody of cell mediated attack against one’s own tissues

Question 39

What is Familial Mediterranean Fever?

Answer 39

Hereditary inflammatory disorder due to mutation in MEFV gene (16p13.3)

Question 40

What are the symptoms of GVHD following an allogeneic stem cell transplant? (5)

Answer 40

 Rash  Nail dystrophy  Liver: Cholestasis and hepatitis  Gut: Anorexia, nausea, vomiting, diarrhea  Bone marrow is not affected; no pancytopenia. This is because there’s no recipient bone marrow cells, so the graft cells are the only cells there

Question 41

Symptoms of DiGeorge Syndrome? (7)

Answer 41

- Parathyroid hypoplasia - Hypocalcemia - Heart malformation: Tetralogy of Fallot, ventricular septal defect - Psychiatric disorders: schizophrenia, anxiety, depression - Thymus hypoplasia: this can cause immune deficiencies o Cytopenia o Thrombocytopenia o Rheumatoid arthritis o Asthma

Question 42

Symptoms of Systemic Lupus Erythematosus? (7)

Answer 42

 Production of ANA antibodies  Mucosal ulcers  Inflammatory arthritis (can come with Jacoud’s Arthropathy)  Lupus nephritis  Serositis: shortness of breath, pleuritic chest pain, fluid accumulation between the heart and the lining of the heart  Hematological problems: anemia, thrombocytopenia, leukomia and lymphopenia  Cutaneous manifestations

Question 43

What are the symptoms of mixed connective tissue disease? (3)

Answer 43

 Raynaud’s phenomenon is common  Lung involvement is common  Production of anti-RNP antibody

Question 44

Clinical manifestations of GVHD following solid organ transplant? (4)

Answer 44

 Skin rash  Fever  Diarrhea, gut dysfunction  Pancytopenia (bone marrow aplasia)