Approach of Primary Immune Deficiencies دکتر افشین شیرکانی فوق تخصص آسم و...
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Transcript of Approach of Primary Immune Deficiencies دکتر افشین شیرکانی فوق تخصص آسم و...
Approach ofPrimary Immune Deficiencies
شیرکانی افشین دکتر
ایمنی نقص های بیماری و آلرژی و آسم تخصص فوقدانشگاه استادیار
آمریکا ایمونولوژی و آلرژی و آسم آکادمی عضو
Comparison of hypersensitivity reactions
reaction
Lymphocyte
Effector cells
Antibody Antigen Time Complement
Diseases
Type I B Eosinophils and basophils
IgE Allergen 15-20 min
- Asthma, atopic dermatitis urticaria
Type II B PMN IgM , IgG Surface Ag
? + Hemolytic disease of newborns
Type III
B PMN IgM, IgG Soluble Ag
6-8 h + SLE
Type IV
T Macrophages
- Intracellular Ag
24-72 h _ Tuberculosis
Immunity Innate & Adaptive
• First line of defense• Nonspecific• Rapid onset• No protective
immunity• No memory• Phagocyte-
mediated
• Activated• Very specific• Slower• Protective immunity
possible• Memory possible• Lymphocyte-
mediated
Definition
• Any defect in the integrity of the immune systems – It may be congenital or late onset– It may be inherited or non hereditary – It may be in innate or adaptive parts of immune
system
Components of Immunity• Skin and mucosal barriers
• Innate immune system (nonspecific)–Phagocytic cells, NK cells, complement
• Adaptive immune system (specific)–T and B lymphocytes, antibodies
Increasing susceptibility to infections
Increasing duration of infections
Increasing severity of infection
Continuous illness
Dependence to antibiotics
Infection with opportunistic agents
Unusual infection
Characteristics of infections
Eight or more new ear infections within 1 year.
Recurrent, deep skin ororgan abscesses.
Two or more serious sinus infections within 1 year.
Persistent thrush in mouth orelsewhere on skin, after age 1.
Two or more months on antibiotics with little effect.
Need for intravenousantibiotics to clear infections.
Two or moredeep-seated infections.
A family history ofPrimary Immunodeficiency.
Two or more pneumonias within 1 year.
Failure of an infant to gainweight or grow normally.
The 10 Warning Signs Of Primary Immunodeficiency
Primary Immunodeficiency
• B cell (Antibody ) system• T cell (cellular ) system• Phagocyte (PMN and mononuclear )• Complement
Classification of Immunodeficiency
1. Humoral (B-cell) – quantitative or qualitative defects in antibody production account for more than 50% of defects.
2. Cellular (T-cell) – usually combined with humoral; account for 20-30%.
3. Phagocytic – defects in migration, or killing; account for ~18%.
4. Complement – account for ~2%
About %40 of cases are diagnosed in the first year
Another %40 by age 5 years
Another %15 by age 16
Only %5 in adulthood
About %10 of registered cases are adults
Late-onset Patients exhibit CVID
• Common Risk Factors for Frequent Infections– Day-care, school– Second-hand smoke– Atopy– Anatomic abnormalities including ciliary
defects– Retained foreign body– Gastroesophageal reflue– Cystic fibrosis
Children referred for evaluation for immuno deficiency
%50 Turn out to be normal
%30 have allergy
%10 have a serious but nonimmunologic
disorder
Only %10 have an immunodeficiency
Allergic disorders in contrast to immunodeficiency
Absence fo fever
Clear nonpurulent discharge
Prior history of colic, food intolerance, ezema or other
allergic symptoms
A Positive family history of allergy
A Characteristic seasonal or exposure pattern
Poor respons to antibiotic
Good respons to antihistamines or bronchodilators
Approach for Suspected Immune Deficiency are as
following:
FAMILY HISTORY
Consanguinity of the parents
History of a sibling dying early in life of infections
Family history of an X-linked or autosomal recessive inheritance of a primary immunodeficiency
GENERAL
• Complete blood count, including hemoglobin, differential white blood cell count(ALC , ANC) and morphology, and platelet count,ESR
• Radiographs to document infection in chest, sinus, mastoids, and long bones, if indicated by clinical history
• Cultures, if appropriate
History Our Guide
• Predominant B-Cell defects– Onset after maternal antibodies diminish, usually
after 5-7 mos, later childhood to adulthood.– Bacteria: strep, staph, H.flu; Campylobacter,
enteroviruses, giardia, cryptosporidia– Recurrent sinopulmonary infections, chronic GI
symptoms, malabsorption, arthritis, viral meningoencephalitis
– Autoimmunity, lymphoreticular malignancy; thymoma, lymphoma
SCREENING TESTS FOR B CELLIMMUNE FUNCTION
• Quantitative serum immunoglobulins• Specific antibodies to vaccine responses• Tetanus, diphtheria (IgG1)• Pneumococcal and meningococcal polysaccharides (IgG2)• Viral respiratory pathogens (IgG1 and IgG3)• Other vaccines: hepatitis B, influenza, MMR, polio (killed vaccine)• Isohemagglutinins (IgM antibodies to A and B blood group• antigens)• B cell quantitation by flow cytometry
Laboratory Evaluation
• Qualitative Evaluation of Antibodies– Isohemagglutins – Antibodies to ABO blood-group
determinants– Antibodies to tetanus and diptheria glycoproteins
and pneumococcal polysaccharides.
• If low titers, give booster, then repeat titers 4 weeks later.
History Our Guide
• Predominant T-Cell Defects– Early onset, usually 2-6 mos– Bacteria, mycobacteria, viruses: CMV, EBV,
varicella; fungi, parasites, PCP, -intracellulare– FTT, diarrhea, extensive mucocutaneous
candidiasis– GVHD caused by nonirradiated blood– Hypocalcemic tetany in infancy(DiGorje)
SCREENING TESTS FOR T CELLIMMUNITY
• Newborn screening for TREC analysis (not available in iran)
• Absolute lymphocyte count• Chest radiograph for thymus shadow in
newborns• Delayed skin hypersensitivity to recall antigens• Quantification of T cell subsets
History Our Guide for B and T cell defficiency
• ATAXIA TELLANGIECTASIA
• SCID
• WISKOTT- ALDERICHE SYNDROME
History Our Guide
• Granulocyte Defects– Early onset, delayed separation of cord (>8 weeks),
poor wound healing(LAD)– Bacteria: staph, Pseudomonas, Serratia, Klebsiella;
Fungi: Candida, Nocardia, Aspergillus(CGD)– Dermatitis, impetigo, cellulitis, abscesses,
lymphadenitis, periodontitis, osteomyelits
History Our Guide
• Complement Defects– Late (C5-C9) – Neisserial infections: meningitidis,
septic arthritis from gonorrhoeae.– Early (C1, C4, and C2) – autoimmune disease– C3 deficiency – overwhelming sepsis, especially
with gram negative organisms
SCREENING TESTS FOR INNATEDEFENSE FACTORS
• Absolute granulocyte count, cell morphology• Serum total hemolytic complement for classic pathway
(CH50), alternative pathway hemolytic activity (AH50)• Nitroblue tetrazolium (NBT) test or flow cytometry
using dihydrorhodamine (DHR) « Staphylococcus aureus, Serratia marcescens, and Aspergillus”
• Flow cytometry for leukocyte adhesion molecules (CD11/CD18
• and CD15a)• IgE (JOB )
B Cell Immunodeficiencies
• Bruton Bruton’ s (X-linked) Agammaglobulinemia• Autosomal Recessive Hyper-IgM Syndrome • X-linked Lymphoproliferative Syndrome• Transient Hypogammaglobulinemia of Infancy• Common Variable Immunodeficiency (CVID)• Selective IgA Deficiency • IgG Subclass Deficiency
General Management of Patients withImmunodeficiency
• Avoid transfusions with blood products unless they are irradiated and cytomegalovirus-negative.
• Avoid live virus vaccines, especially in patients with severe T-cell deficiencies or agammaglobulinemia, and in household members.
• Use prophylaxis to Pneumocystis jiroveci (carinii) in T-cell immunodeficiency, and in X-linked hyper-IgM, consider antifungal prophylaxis in T-cell immunodeficiency.
• Follow pulmonary function in patients with recurrent pneumonia.
• Use chest physiotherapy and postural drainage in patients with recurrent pneumonia.
• Consider using prophylactic antibiotics because minor infections can quickly disseminate.
• Examine diarrheal stools for Giardia lamblia and Clostridium difficile.
• Avoid unnecessary exposure to individuals with infection.
• Boil water for T-cell defects and hyper-IgM syndrome (Cryptosporidium risk).
• Use immunoglobulin for severe antibody deficiency states (400–600mg/kg q3–4 wk IV).
• BMT for T cell and Innate defect
When IgG level are normal or near normal but Antibody deficiency is susceptible
IgG subclasses should be measured (IgG=70%, IgG 2 =20%, IgG3=7%, IgG4=3%)
Antibody function should be measured
In patient with selective IgA deficiency IgG subclasses should be measured
Many IgA deficiency patients have IgG2 subclass deficiency
In older children and adults , a total Ig level above 800 mg/ dl with normal screening antibody test excludes antibody deficiency
Total Ig (IgG+IgM +IgA )< 400 or IgG level <200 mg /dl usually indicates antibody immunodeficiency