PRIMARY SECONDARY IMMUNODEFICENCIES doi 10 1016j iac 2015

PRIMARY & SECONDARY IMMUNODEFICENCIES doi: 10. 1016/j. iac. 2015. 07. 001 Stiehm, Ochs Dr. Yıldıran 1

DEFINITION • If the immune system cannot work properly: – Immune dysregulation • Autoimmune disorders (more than 100) • Allergy (30% in somewhere) – Immune deficiencies • Primary (more than 340 disease) • Secondary (more common) Dr. Yıldıran 2

DEFINITION • Increased susceptibility to infections. • Heterogeneous: – Recurrent infections, – Autoimmunity, – Lymphoproliferation, – Ganulomatous process, – Atopy – Malignancy Dr. Yıldıran 3

Common Infection • In one year: – More than two severe infections – More than three RTI (sinusitis, otitis, bronchitis) – Antibiotic need more than two months Stiehm, Uptodate, 2012 Dr. Yıldıran 4

Think immunodeficiency Buckley, IDF, 2009 Dr. Yıldıran 5

SOME CLUES • Bacterial infections - B cell defects. • Infections with diverse pathogens (e. g. , viruses, fungi, and bacteria) - combined T and B cell • Lymphoproliferation- XLPS, ALPS • Cutaneous, respiratory, or gastrointestinal tract granulomas - CGD. • Asthma, atopic dermatitis, and food allergies - T cell defects. Dr. Yıldıran 6

Main physiologic barriers Hydrochloric acit Ciliar epithelia Tears Normal flora Dr. Yıldıran 7

Postnatal Immunglobulin level changes Ig. G Mean serum immunglobulin level (mg/dl) Maternal Ig. G (in child) (ço Ig. A Ig. M Month Birth Month Dr. Yıldıran Age Year Y 8

ESID Classification Primary Immunodeficiencies 1 Predominantly T cell deficiencies 2 Antibody deficiencies 3 Other well defined immundeficiencies 4 Complement deficiencies 5 Phagocytic disorders 6 Autoimmune and immundysregulation disorders 7 Autoinflammatory diseases Dr. Yıldıran 9

PID Samples • Bruton diseases: Agammaglobulinemia. BTK • SCID: T cells absent- RAG, JAK 3, IL 2 R • Hereditary Angioedema: C 1 inh • CVID: B cell dysfunction- CD 19, CD 20, TACI • Di George Syndrome: 22 q 11 del • CGD: NADPH oxidase deficiency • FMF: MEFV Dr. Yıldıran 10

PID Samples • • IPEX- Foxp 3 APECED- AIRE ALPS- Fas, Fas. L Hiper. Ig. M syndrome- CD 40, CD 40 L • The most common PID is selective Ig. A deficiency and CVID Dr. Yıldıran 11

Chronic granulomatous disease Dr. Yıldıran 12

Secondary ID • • • Hemoglobinopathy Malnutrition • Neurological dis. Stress Diabetes mellitus Ischemic artery disease HIV infection Cirrhosis Nephrotic syndrome Intestinal lymphangiectasis Stiehm, Uptodate, 2012 Dr. Yıldıran 13

AIDS • HIV destroys CD 4 T cells (adaptive immunity!) • Virus contaminates from blood products, sexually or vertically in delivery of newborn. Dr. Yıldıran 14

Ten signs of PID Dr. Yildiran 15

Dr. Yildiran 16

The need for immunological evaluation • • Common infection Recurrent absscess Persistent moniliasis Persistent diarrhea Prolonged and/or severe infection Unusual pathogen Illness after live vaccine Dr. Yildiran 17

• • • Failure to thrive Delayed wound healing Delayed drop of newborn umbilicus Chronic lung disease/ bronchiectasis Family history Abnormal laboratory findings: – Lymphopenia, – neutropenia, – eosinophilia, – thrombocytopenia, – hypogammaglobulinemia Dr. Yildiran 18

CHECK FIRST! • CBC • TLS <3 year >3000/mm 3 • Serum Ig. AME levels Dr. Yildiran 19

MHC I

HPV

OMENN

ALPS

APECED

IPEX

HİPER Ig. E

CGD

LAD veya Kostman

E. K. Mart 2010