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Stewart.k BDS 2
Fiji school of medicine.
 What is leukocyte adhesion deficiency
 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
 The hallmarks of leukocyte adhesion deficiency syndrome
(LAD) are the defects in the leukocyte adhesion process
marked leukocytosis and recurrent infection.
 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
 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.
 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
Theyuponcontinually circulate
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

Pathophysiology-How leukocytes works.

How leukocyte work.4 steps.
Step 1. gathering and rolling.
Step 2.activation
Step adhesion
Step 4.trasmigration,chemotaxis.
 Types surface protiens needed for the
adhesion of leukocytes are:
 Mucins
 Intergrins- CD18,CD11a,CD11b
 Selectins- P-selectins,E-Selectins
 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..
 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.
 Is an autosomal recessive disorder in which the
patient have a mutation in the gene coding CD18.
 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
 Most patients express no CD18 on lymphocytes,
neutrophils and macrophages.
 Affects mostly children
 Very rare affects 1 in every 100,000 births
 USA less than 200, & worldwide
 Bacterial species involved-staphylococcus species,
gram (-) bacteria,
 Fungal organism-candidas speciese.
Clinical manifestation.LAD 1
 Recurrent viral and life threatening
bacterial infection.
 Infections are:
abscesses, peritonitis
 Impaired wound healing-skin and
mucous membrane.
 Recurrent oral ulceration
 Rapidly progressing periodontal disease
 Linear gingival erythma

 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
 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.
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
Ulceration on the attached gingiva on a child with chronic
granulomatous disease.the ulcer healed without scarring.
 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.
 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
 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
 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.
 New man t., 2006, Clinical Periodontology,
10th edition, saunders,carranza
 Goldman. a, 2008,Cecil Medicine, 23th
edition, Saunders Elsevier,
 Neville's., 1998, Pathology and Basic &Systemic,
 . Etzioni,2005,Leukocyte Adhesion Deficiency
(LAD), Orphaned Encyclopedia,\data\patho\GB\uk-leukocyte adhesion
, 09\07\09
 10. Stephen j. ,2007, Leukocyte Adhesions
deficiency,www.emedicine/leukocyte adhesion
 11., 2003, Blood, LAD3,
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