Sandbox:Zahir

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2]

Algorithm

Diseases Of Immune Dysregulation:(A) Hemophagocytic Lymphohistiocytosis (HLH) & EBV Susceptibility

Hemophagocytic Lymphohistiocytosis(HLH)

Susceptibility to EBV

Hypopigmentation

Familial Hemophagocytic Lymphohistiocytosis Syndromes

EBV Associated with HLH

Chediak Higashi Syndrome:LYST

Perforin Deficiency(FHL2)

RASGRP1 Deficiency

XL,XLP1.SH2DIA

Griscelli Syndrome type2:RAB27a

UNCBD/Munc13-4 deficiency(FHL3)

CD70 Deficiency

XL,XLP2,XIAP

Hermansky Pudlak Syndrome type2:AP3B1

Syntaxin II Deficiency(FHL4)

CTPS1 Deficiency

AR, CD27 Deficiency

Hermansky Pudlak Syndrome type10

STXBP2/Munc18-2 Deficiency

RLTPR (CARMIL2) Deficiency

FAAP24 Deficiency

ITK Deficiency

MAGT1 Deficiency

PRKCD Deficiency

Pathophysiology

Pathology

• AAA
• BBB
  • CCC

• abc
• def

Diseases		A	B
ABC	Type 1
	Type 2
DEF

Algorithm

Combined Immunodeficiencies Generally Less Pronounced than Severe Combined Immunodeficiency

Low CD4: MHC II Expression?

Low CD8

Low B Cells

Ig: Often Normal

Ig Low

Normal Ig but Low Specific Antibody Response

Absent: MHCII Deficiency

Present: XL: MAGT 1 Def:, AR: LCK Def:, AD: UNC119 Def:

IL2IR Def:

MALT1 Def:

CD8 def:

ZAP70 def:

MHC1 def:

DOCK8 def:

MST1 def:

IL21 def:

NIK def:

Moesin def:

CD3Y def:

RHOH def:

TCR alpha def:

BCL11B def:

OX40 def:

LAT def

DOCK2 def:

CARDII def:(LOF)

BCL10 def:

IKBKB Def:

ICOS def:

TFRC def:

RelB def:

CD40 ligand def:(CD154)

Algorithm

Diseases of Immune Dysregulation: (B) Syndromes with Autoimmunity and Others

Syndromes with Autoimmunity

Immune Dysregulation with Colitis: IBD, Normal Tc & Bc

Increased CD4-CD8-TCR alpha/beta (Double Negative T cells)

IL10 Deficiency, IL10, AR

Yes

Occassionally

NO: Regulatory T cells Defects?

IL10Ra Deficiency, IL10RA, AR

ALPS, Autoimmune Lymphoproliferative Syndrome

LRBA Deficiency

NO

YES

IL10Rb Deficiency, IL10RB, RA

ALPS-FAS TNFRSF, AD or AR

STAT3 GOF mutation,STAT3 AD

Autoimmune Polyendocrinopathy with candidiasis & ectodermal dystrophy: APECED (APS-1)

IPEX Immune dysregulation, Polyendocrinopathy,enteropathy,X-linked FOXP-3

NFATS haploinsufficiency, NAFTS, AD

ALPS-FASLG TNFSF6, AR

ITCH Deficiency, ITCH, AR

CD25 Deficiency, IL2RA, AR

ALPS-Caspase10, Casp10, AD

ZAP70 combined hylomorphic and activation mutations, ZAP70, AR

CTLA4 deficiency (ALPSV) CTLA4, AD

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