PAEDIATRIC IMMUNOLOGY
Primary Immunodeficiencies
Severe combined
B-cell immunodeficiency T-cell disorders immunodef. Syndrome Phagocytic disorder Complement disorder
(SCID)
Epi Most severe 25% of PID
most common – 55% of PID 9% of PID 12.5% of PID
Age Ø Present at 3-6/12 of life (as 1st year of life 1st mths of life Normally diagnosed at SLE,
maternal Abs decrease) 5yo
PP Cannot produce antibodies causing Abnormal or absent T cells Abnormal or absent B and T = no phagocytes = no Ø C2 def – most
hypogammaglobulinemia Ø CD4 = cytokine release cells removal of catalse +ve common
Ø Cd8 = Lyse virus infected or organism (e.g. S. aureus, Ø C1 esterase
cancer cells aspergillus, serratia, inhibitor def.
Selective Immunoglobulin A def. Causes: candida)
DiGeorge syndrome (22q11.2) (hereditary
Ø Most common Ø JAK3 mutation angioedema) -no
Ø Congenital heart disease
Ø Low IgA levels (normal IgM, Ø Abnormal facies Ø Adenosine deaminase inhibition of
IgG) Ø Thymus underdeveloped def. bradykinin release
(no functional T cells) during inflammatory
Ø Unable to protect against Ø Omenn syndrome - X- response
opportunistic infections of MM Ø Cleft palette linked recessive
(e.g. LRTi, autoimmune) Ø HypoPTH - hypoCa mutation of RAG ½ Ø Mannose binding
Ø 22 chr lectin def
*NB: coeliac disease (falsely normal (dysfn T cells attack
fetus and neonate)
IgA-TTG and IgA-EMA) ® need to Purine nucleoside phosphorylase
test IgG versions def.
Ø Autosomal recessive
Ø Def. of PNPase enzyme to
Common variable immunodef.. breakdown purines –
Ø Genetic mutation encoding increases dGTP levels
components of B cells Ø Lowers T cell levels
Ø Low IgA, IgG (normal IgM)
Sx Ø No immunity to infections of Wiscott-Aldrich (WAS gene) • Persistent severe Chronic granulomatous Ø Risk of
vaccinations Ø Thrombocytopenia diarrhoea disease: encapsulated
Ø Neutropenia Ø recurrent soft- organism (Strep,
Ø High risk of cancers (NHL) and • FTT
Ø Eczema tissue infection by pneumoniae, HiB,
autoimmune (RA)
Ø Recurrent infections • Opportunistic Neisseria) –
bacteria and fungi
Ø Rx: IVIg infection (E.g. PJP, normally dealt with
® leads to IBD
CMV, chicken pox) by complement
Ataxia telangiectasia Ø pneumonia,
X-linked agammaglobulinemia • Unwell after vax Ø Unexplained
Ø Autosomal recessive abscess,
Angioedema esp.
Ø AKA “Bruton’s Ø ATM serine/threonine kinase suppurative
lipi swelling for C1
agammaglobulinemaia” protein on Chr 11 adenitis, GIT
esterase inhibitor
Ø Recurrent infection (low T infections,
Ø X-linked recessive Omenn syndrome omphalitis (1st sign) def.
cell)
(check C4 levels =
Ø Deficiency in all class of Ig Ø Ataxia – uncoordinated Ø Erythroderma (red low)
movement scaly, dry rash)
Ø Telengiectasia – esp. sclera
Ø Alopecia
and skin damage
Ø Cancer risk (esp. haem Ø Diarrhoea
cancers) Ø FTT
Ø Stunted growth
Ø Accelerated ageing Ø LN
Ø HSM
AIDS (acquired immunodef.
Syndrome)
Mx Ø Abx for early infection Haematopoietic stem cell transplant Urgent specialist paediatric Abx for early infection Abx for early infection
Ø IVIg (SC at home) (curative intent) immunologist Vaccinate against
• IVIg encapsulated
• Sterile environment –
minimise risk of new
infections
• HSCT
DDx of recurrent infections: General work up for PID or RECURRENT INFECTIONS
1. Anatomical defect (e.g. nasal defect Ø FBC
= recurrent sinusitis) Ø Low lymphocytes = T cell disorder
2. Organic = cystic fibrosis (LRTi) Ø Low neutrophils = phagocytic
3. Extrinsic = inhaled foreign objects Ø Low plts = Wiskott-Aldrich
SIGNS: Ø Flow cytometry
Ø Chronic diarrhoea since infancy Ø Serum complement (C3-C9)
Ø FTT Ø HIV testing
Ø Unusually well despite infection
Ø Serum Ig (A/B/G/M/E) + albumin (is it renal issue,
Ø Unusual pathogens (CMV, candida)
protein malabsorption)
Other
*Secondary (acq. immunodeficiencies):
*Nb: normal for a healthy child to 1. immunosuppressive drugs
Ø CXR – scarring from previous chest infections
Ø Sweat test (CF)
have 4 – 8 respiratory infections 2. malnutrition Ø CT scan chest (bronchiectasis)
per year. 3. trauma/surgery/indwelling lines
4. splenectomy
5. chronic disease
6. AIDs
Primary Immunodeficiencies
Severe combined
B-cell immunodeficiency T-cell disorders immunodef. Syndrome Phagocytic disorder Complement disorder
(SCID)
Epi Most severe 25% of PID
most common – 55% of PID 9% of PID 12.5% of PID
Age Ø Present at 3-6/12 of life (as 1st year of life 1st mths of life Normally diagnosed at SLE,
maternal Abs decrease) 5yo
PP Cannot produce antibodies causing Abnormal or absent T cells Abnormal or absent B and T = no phagocytes = no Ø C2 def – most
hypogammaglobulinemia Ø CD4 = cytokine release cells removal of catalse +ve common
Ø Cd8 = Lyse virus infected or organism (e.g. S. aureus, Ø C1 esterase
cancer cells aspergillus, serratia, inhibitor def.
Selective Immunoglobulin A def. Causes: candida)
DiGeorge syndrome (22q11.2) (hereditary
Ø Most common Ø JAK3 mutation angioedema) -no
Ø Congenital heart disease
Ø Low IgA levels (normal IgM, Ø Abnormal facies Ø Adenosine deaminase inhibition of
IgG) Ø Thymus underdeveloped def. bradykinin release
(no functional T cells) during inflammatory
Ø Unable to protect against Ø Omenn syndrome - X- response
opportunistic infections of MM Ø Cleft palette linked recessive
(e.g. LRTi, autoimmune) Ø HypoPTH - hypoCa mutation of RAG ½ Ø Mannose binding
Ø 22 chr lectin def
*NB: coeliac disease (falsely normal (dysfn T cells attack
fetus and neonate)
IgA-TTG and IgA-EMA) ® need to Purine nucleoside phosphorylase
test IgG versions def.
Ø Autosomal recessive
Ø Def. of PNPase enzyme to
Common variable immunodef.. breakdown purines –
Ø Genetic mutation encoding increases dGTP levels
components of B cells Ø Lowers T cell levels
Ø Low IgA, IgG (normal IgM)
Sx Ø No immunity to infections of Wiscott-Aldrich (WAS gene) • Persistent severe Chronic granulomatous Ø Risk of
vaccinations Ø Thrombocytopenia diarrhoea disease: encapsulated
Ø Neutropenia Ø recurrent soft- organism (Strep,
Ø High risk of cancers (NHL) and • FTT
Ø Eczema tissue infection by pneumoniae, HiB,
autoimmune (RA)
Ø Recurrent infections • Opportunistic Neisseria) –
bacteria and fungi
Ø Rx: IVIg infection (E.g. PJP, normally dealt with
® leads to IBD
CMV, chicken pox) by complement
Ataxia telangiectasia Ø pneumonia,
X-linked agammaglobulinemia • Unwell after vax Ø Unexplained
Ø Autosomal recessive abscess,
Angioedema esp.
Ø AKA “Bruton’s Ø ATM serine/threonine kinase suppurative
lipi swelling for C1
agammaglobulinemaia” protein on Chr 11 adenitis, GIT
esterase inhibitor
Ø Recurrent infection (low T infections,
Ø X-linked recessive Omenn syndrome omphalitis (1st sign) def.
cell)
(check C4 levels =
Ø Deficiency in all class of Ig Ø Ataxia – uncoordinated Ø Erythroderma (red low)
movement scaly, dry rash)
Ø Telengiectasia – esp. sclera
Ø Alopecia
and skin damage
Ø Cancer risk (esp. haem Ø Diarrhoea
cancers) Ø FTT
Ø Stunted growth
Ø Accelerated ageing Ø LN
Ø HSM
AIDS (acquired immunodef.
Syndrome)
Mx Ø Abx for early infection Haematopoietic stem cell transplant Urgent specialist paediatric Abx for early infection Abx for early infection
Ø IVIg (SC at home) (curative intent) immunologist Vaccinate against
• IVIg encapsulated
• Sterile environment –
minimise risk of new
infections
• HSCT
DDx of recurrent infections: General work up for PID or RECURRENT INFECTIONS
1. Anatomical defect (e.g. nasal defect Ø FBC
= recurrent sinusitis) Ø Low lymphocytes = T cell disorder
2. Organic = cystic fibrosis (LRTi) Ø Low neutrophils = phagocytic
3. Extrinsic = inhaled foreign objects Ø Low plts = Wiskott-Aldrich
SIGNS: Ø Flow cytometry
Ø Chronic diarrhoea since infancy Ø Serum complement (C3-C9)
Ø FTT Ø HIV testing
Ø Unusually well despite infection
Ø Serum Ig (A/B/G/M/E) + albumin (is it renal issue,
Ø Unusual pathogens (CMV, candida)
protein malabsorption)
Other
*Secondary (acq. immunodeficiencies):
*Nb: normal for a healthy child to 1. immunosuppressive drugs
Ø CXR – scarring from previous chest infections
Ø Sweat test (CF)
have 4 – 8 respiratory infections 2. malnutrition Ø CT scan chest (bronchiectasis)
per year. 3. trauma/surgery/indwelling lines
4. splenectomy
5. chronic disease
6. AIDs
