1. JENIFER RASEETHA
M.Sc. PART- I
PSBT - 202
CHRONIC GRANULOMATOUS DISEASE(CGD)
AND
LEUKOCYTE ADHESION DEFICIENCY (LAD)

2. CHRONIC GRANULOMATOUS DISEASE(CGD ):
• CGD is an inherited disorder in which neutrophil’s phagocytic
function do not work properly.
• Also known as Bridges–Good syndrome,Chronic granulomatous
disorder, and Quie syndrome.
• It was first recognized in 1954.
• TYPES OF CGD:
• CGD has atleast 2 distinct forms:
i. X-linked form (70% of patients)
ii. Autosomal recessive form.

4. MECHANISMS OF PHAGOCYTOSIS :

5. WHO GETS CGD:
 NADPH oxidase (gp91-PHOX) is an enzyme which produce reactive
oxygen species.
1. It is vital for phagocyte killing of bacteria.
2. Defects in 1 of the 4 essential subunits of the enzyme cause CGD.
• A defect or missing cytochrome (cyt b558-CYBA) can cause CGD.
• Mononuclear cells ability to serve asAPC’s is decreased, processing
and presentation of antigen is impaired.

6. • Osteomyelitis (Bone infections).
• Frequent and difficult-to-clear skin infections.
• Pneumonia.
• Swollen lymph nodes.
• Gingivitis.
• Non malignant granulomas.
SYMPTOMS :
• Bone scan
• Chest x-ray
• Complete blood count
• Flow cytometry tests
• Nitroblue tetrazolium test (NBT)
• Cytochrome C reduction assay.
DIAGNOSIS :
• Antibiotics -Trimethoprim-sulfamethoxazole for
bacteria and Itraconazole for fungi.
• Immunomodulation - Interferon gamma-1b
• Hematopoietic stem cell transplantation
• Gene therapy – Replacement of defective cytochrome
TREATMENT:

7. RECENT RESEARCH :
 Uric acid induces NADPH oxidase-independent neutrophil
extracellular trap formation.

8. LEUKOCYTEADHESION DEFICIENCY (LAD) :
 LAD is a rare autosomal recessive disorder characterized
by immunodeficiency resulting in recurrent infections.
 It was first recognized as a distinct clinical entity in the 1970s.
 TYPES OF LAD :
 Three LAD syndromes have been described and a fourth category of
newly-described defect is also being reviewed.
1. LAD I - the beta 2-integrin family is deficient or defective
2. LAD II - the fucosylated carbohydrate ligands for selectins are
absent
3. LAD III - activation of all beta–integrins (1, 2, and 3) is defective
4. Other defects of neutrophil adhesion.

9. LAD-I
• Results due to defect in expression of 3 integrin family protein.
• LFA –I, Mac-1, gp 150/95 ( CD a,b,c) respectively.
• These are αβ heterodimers and have a common β chain.( CD18).
• Failure to express CD18 (ITGB2).
LAD-II
• Defect in the expression of ligands for selectins (SLC35C1).
• Thus defect in fucose metabolism.
• Patients have leukocytosis, recurrent infections , and severe growth
and mental retardation.
LAD-III
• Defect in activation of all beta–integrins (1, 2, and 3)
• Defect in FERMT3 gene.

10. • Omphalitis
• Pneumonia
• Gingivitis
• PeritonitisSYMPTOMS:
• Several preliminary tests of immune function
• WBC differential
• Monoclonal antibody testing for CR3DIAGNOSIS :
• Bone marrow transplantation
• Interferon-gamma, and leukocyte transfusions
• Gene therapy with insertion of the CD18
• Fucose replacement for LAD IITREATMENT:

11. RECENT RESEARCH :
• Long-term follow-up of foamy viral vector-mediated
gene therapy for canine leukocyte adhesion deficiency.

12. REFERENCE :
 CHRONIC GRANULOMATOUS DISEASE (CGD) :
 Quie PG,White JG, Holmes B, Good RA: In vitro bactericidal capacity of human polymorphonuclear leukocytes:
diminished activity in chronic granulomatous disease of childhood. J Clin Invest 1967, 46(4):668-679.
 Baehner RL, Karnovsky ML: Deficiency of reduced nicotinamide-adenine dinucleotide oxidase in chronic
granulomatous disease.Science 1968, 162(859):1277-1279.
 Hohn DC, Lehrer RI: NADPH oxidase deficiency in X-linked chronic granulomatous disease. J Clin
Invest 1975, 55(4):707-713.
 Curnutte JT,Whitten DM, Babior BM: Defective superoxide production by granulocytes from patients with
chronic granulomatous disease.N Engl J Med 1974, 290(11):593-597.
 LEUKOCYTE ADHESION DEFICIENCY (LAD):
 Harlan JM, Killen PD, Senecal FM, et al.The role of neutrophil membrane glycoprotein GP-150 in neutrophil
adherence to endothelium in vitro. Blood 1985; 66:167.
 Mathew EC, Shaw JM, Bonilla FA, et al.A novel point mutation in CD18 causing the expression of dysfunctional
CD11/CD18 leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD). Clin Exp Immunol 2000;
121:133.
 Hogg N, Stewart MP, Scarth SL, et al.A novel leukocyte adhesion deficiency caused by expressed but
nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest 1999; 103:97.
 RESEARCH:
 AraiY1, NishinakaY2,AraiT3, Morita M4, Mizugishi K1,Adachi S4,Takaori-KondoA1,WatanabeT5,Yamashita
KUric acid induces NADPH oxidase-independent neutrophil extracellular trap formation. Biochem Biophys Res
Commun. 2014 Jan 10;443(2):556-61. doi: 10.1016/j.bbrc.2013.12.00.
 BauerTR Jr,Tuschong LM, Calvo KR, Shive HR, BurkholderTH, Karlsson EK,West RR, Russell DW, Hickstein
DD. Long-term follow-up of foamy viral vector-mediated gene therapy for canine leukocyte adhesion deficiency.
2013 May;21(5):964-72. doi: 10.1038/mt.2013.34.