- 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 neutrophils phagocytic function do not work
properly. Also known as BridgesGood 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. 3. MECHANISMS OF
PHAGOCYTOSIS : 4. 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
asAPCs is decreased, processing and presentation of antigen is
impaired. 5. 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: 6. RECENT RESEARCH : Uric acid
induces NADPH oxidase-independent neutrophil extracellular trap
formation. 7. 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 betaintegrins (1, 2, and 3) is defective 4.
Other defects of neutrophil adhesion. 8. 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 heterodimers and have a
common 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 betaintegrins (1, 2, and 3) Defect in
FERMT3 gene. 9. 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: 10. RECENT RESEARCH : Long-term
follow-up of foamy viral vector-mediated gene therapy for canine
leukocyte adhesion deficiency. 11. 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.
