Leukocyte Adhesion Deficiency Syndrome

LEUKOCYTE ADHESION DEFICIENCY SYNDROME. Stewart.k BDS 2 Fiji school of medicine.

Objectives. 

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What is leukocyte adhesion deficiency syndrome. Pathophysiology Pathogenesis How does it leads to periodontitis How it affects treatment

1.What is leukocyte adhesion deficiency syndrome. 

Leukocyte adhesion deficiency syndrome(LAD) a rare autosomal recessive disorder characterized by recurrent infection.

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The hallmarks of leukocyte adhesion deficiency syndrome (LAD) are the defects in the leukocyte adhesion process marked leukocytosis and recurrent infection.

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These molecular and clinical manifestations results an impaired step in the inflammatory process, namely the emigrations of leukocytes from the blood vessels to the site of infection which requires adhesion of leukocytes to the endothelium.

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There are three types-(LAD1-3).type 1and 2 are clearly autosomal recessive disorder, while the mode of transmission for type 3 is still unknown.

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First recognized in 1970s

Leukocytes are white blood cells that are derived from myeloid cells in the bone marrow. They play an important role in the body's defense. They circulate uponcontinually infection,inflamation or in the blood vessel infaction,cytokines are released to the

endothelial cells on the blood vessels. They then release surface proteins called selectins. The selectins binds to the carbohydrate on the surface of the leukocyte causing them to roll along the cell finding nearest point of exit. They then enter through to the site of infection

Pathophysiology-How leukocytes works.

How leukocyte work.4 steps. Step Step Step Step

1. gathering and rolling. 2.activation 3.film adhesion 4.trasmigration,chemotaxis.

Cont. 

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Types surface protiens needed for the adhesion of leukocytes are: Mucins Intergrins- CD18,CD11a,CD11b ICAMS- ICAM1,ICAM2 Selectins- P-selectins,E-Selectins

WHAT HAPPENS IN LAD. 

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A hereditary disorder of granulocyte movement, or Defective or absent expression of adhesion molecules (CD11 and CD 18) on the surface of neutrophils. This decreases their adhesion to endothelial cells and prevents their migration to sites of infection. The disease is very rare ,often occur in children of consanguineous marriage.

Causes of LAD..  

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1. mutation 2. Drugs. 2 common drugs are; Epinephrine& corticosteroid. 3. Autonomic recessive genetic disorder.

Autonomic recessive genetics. TThe inherited molecular defect in patients with LAD is a deficiency of the β-2 integrin subunit, also called CD18, of the leukocyte cell adhesion molecule, which is found on chromosome 21.

TYPE 1. 

Is an autosomal recessive disorder in which the patient have a mutation in the gene coding CD18.

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the result is a deficiency of beta 2 intergrin receptors which are required for neutrophils migration from the vasculature into the tissue, thereby impairing the binding of neutrophils to c3b and endothelial ICAM-1 and ICAM-2

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Most patients express no CD18 on lymphocytes, neutrophils and macrophages.

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Affects mostly children

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Very rare affects 1 in every 100,000 births

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USA less than 200, & worldwide

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Bacterial species involved-staphylococcus species, gram (-) bacteria,

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Fungal organism-candidas speciese.

Clinical manifestation.LAD 1 

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Recurrent viral and life threatening bacterial infection. Infections are: omphalitis,pneumonia,gingivitis, abscesses, peritonitis Impaired wound healing-skin and mucous membrane. Recurrent oral ulceration Rapidly progressing periodontal disease Linear gingival erythma

TYPE 2.LAD2 

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neutrophils fail to express the ligand (CD 15) for P-selectins and E-selectins, resulting in impaired transendothelial migration in response to inflamation”clinical periontology pg236. It is extremely rare with only 10 cases reported in brazil and middle east.

Clinical manifestation..LAD 2     

Mental retardation Impared facial growth Limp malformation Short stature Severe developmental delay

Type 3. 

still unclear whether it is an autosomal recessive disorder or not. It involves a general defect in intergrin beta’s 1,2&3.The intergrin subunits have been observed and it seems that it may be due to several defects in the molecules involved in the intergrin activation.

Clinical manifestation 

. Its clinical manifestations are somewhat similar to that of LAD1 but also includes severe bleeding tendency starting at delivery or later.

Lad-clinical manifestations. Mucosal ulceration that healed with scarring on lower lip of this child who has leukocyte adhesion deficiency.

Cont,,,… Marked linear gingival erythma in a child with leukocyte adhesion deficiency syndrome.

Rapidly progrssing aggressive PERIODONTITIS in a 5yr old girl with LAD.all primary teeth exhibted 50% bone at the time of examination.

Cont… Ulceration on the attached gingiva on a child with chronic granulomatous disease.the ulcer healed without scarring.

DIAGNOSIS 

These recessive disorder is detrimental especially in childhood for the type. Yet it can be diagnosed by the following. For LAD type 1 flow cytometry is used to measure CD11\CD18-cell adhesion molecules-surface expression levels on neutrophils.the type 2 LAD is confirmed by the flow cytometry for CD15.

TREATMENT 

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Oral Antibiotics - usually used for maintaining the day-to-day health of the patient.   Intravenous Antibiotics - usually used when the patient suffers from a severe infection.   White Blood Cell Transfusions - again usually suggested when the patient suffers from a severe infection. Other treatments are usually used first since this treatment can have potentially significant adverse side effects.   Bone Marrow or Stem Cell Transplants - this is usually the treatment of last resort because of life-threatening nature of the procedure. However, this is currently the best chance that some L.A.D. patients have at a normal quality of life because it comes closest to a cure for L.A.D. But we must emphasize that the potential benefits must be carefully weighed against the risks and costs. Permanent Gene Therapy - the best future hope for L.A.D. patients. The ability to actually replace the defective gene and provide normal quality of life. At last we heard, the ability to permanently replace a defective gene was 3-5 years away, but we're still hopeful that this is a conservative estimate.

Conclusion. 

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There three types of this hereditary disorder. And type one is the more common and severe of the three. They have similar clinical manifestations and in dentistry aggressive periodontitis and gingivitis with tooth loss is present. Also in treating a patient in any dental procedure firstly recurrent infection should be controlled with prophylactic antibiotics. Blood transfusion should also be addressed as well as granulocyte transfusion and bone marrow transplantations as the last resort.

REFERENCE. 

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New man t. et.al, 2006, Clinical Periodontology, 10th edition, saunders,carranza Goldman. a et.al, 2008,Cecil Medicine, 23th edition, Saunders Elsevier, Neville's., 1998, Pathology and Basic &Systemic, . Etzioni,2005,Leukocyte Adhesion Deficiency (LAD), Orphaned Encyclopedia, www.orphc.net\data\patho\GB\uk-leukocyte adhesion , 09\07\09 10. Stephen j. ,2007, Leukocyte Adhesions deficiency,www.emedicine/leukocyte adhesion deficiency.pdf,13/07/09 11. KInashi.t.et.al, 2003, Blood, LAD3,

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