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FVIST
90121
HMDP
89220
Adults 8:00 AM Upright 5-46 TEST PERFORMED BY ESOTERIX
ENDOCRINOLOGY 4301 LOST HILLS ROAD CALABASAS
HILLS, CA 91301
Hydroxyzine (Vistaril, Atarax), Serum
Reference Values:
Reference Range: 10-100 ng/mL
Test Performed by: Medtox Laboratories, Inc.
402 W County Road D
St. Paul, MN 55112
Hyperimmunoglobulin M (Hyper-IgM) Defects Panel
Clinical Information: Hyperimmunoglobulin M (hyper-IgM) syndromes are a collection of primary
humoral immunodeficiencies characterized by recurrent infections along with low serum IgG and IgA,
and normal or elevated IgM. Over the course of the last several years, at least 5 genetic defects have been
shown to be associated with this group of immunodeficiencies.(1-3) These genetic defects include
mutations that affect: -The costimulatory molecule, CD40LG, induced on activated T cells -The CD40LG
receptor, CD40, expressed constitutively on B cells -Activation-induced cytidine deaminase (AID or
AICDA), involved in somatic hypermutation (SHM) and isotype class-switching -Uracil DNA
glycosylase (UNG), also involved in isotype class-switching and partially in SHM -NF-kappa B essential
modulator (NEMO), also known as IKK gamma, which modulates NF-kappa B function(2,3) The
mutations that occur in the CD40LG and CD40 genes are associated with X-linked hyper-IgM (type 1)
and autosomal recessive hyper-IgM (type 3), respectively. Patients with mutations in either of these 2
genes are particularly prone to infections with opportunistic pathogens, such as Pneumocystis jiroveci,
Cryptosporidium parvum, and Toxoplasma gondii.(4) All of the hyper-IgM syndromes (except those due
to UNG defects and a hitherto undefined autosomal recessive [non-type 3] hyper-IgM) are associated with
defects in isotype class-switching and SHM.(4) In the undefined autosomal recessive hyper-IgM there is
no SHM defect, and in UNG deficiency there is biased SHM.(4) The impairment in isotype
class-switching leads to the increased IgM levels with corresponding decrease in the "switched''
immunoglobulins such as IgG, IgA, and even IgE. In the adult patient, hyper-IgM syndromes can overlap
clinically with common variable immunodeficiency (CVID). However, patients with CD40LG (X-linked
hyper-IgM; HIGM1) and CD40 (hyper-IgM type 3; HIGM3) mutations invariably present in infancy with
upper and lower respiratory tract infections and opportunistic infections as previously described. HIGM1
is the most common of all the hyper-IgM syndromes described thus far, while HIGM3 is much more rare.
Intermittent neutropenia is common in HIGM1 and has also been reported for HIGM3. Both diseases
show significant decreases in class-switched memory (CD27+IgM-IgD-) B cells, corresponding to
profound reductions in serum IgG and IgA levels. Peripheral T-cell subsets are normal, though in HIGM1
the number of CD45RO+ memory T-cells is reduced. T-cell lymphocyte proliferative responses to
mitogens are normal in both HIGM1 and HIGM3, while responses to specific antigen are abnormal in
HIGM1 and normal in HIGM3. TBBS/9336 T- and B-Cell Quantitation by Flow Cytometry and
IABC/87994 B-Cell Phenotyping Screen for Immunodeficiency and Immune Competence Assessment,
Blood evaluate isotype class-switching defects with identification of various memory B-cell subsets,
including class-switched memory B cells. The other components of this panel include the CD40LG
XHIM/82964 X-linked Hyper IgM Syndrome, Blood, and CD40/89009 B-Cell CD40 Expression by Flow
Cytometry, Blood, the CD40 assay for HIGM3. The absolute counts of lymphocyte subsets are known to
be influenced by a variety of biological factors, including hormones, the environment and temperature.
The studies on diurnal (circadian) variation in lymphocyte counts have demonstrated progressive increase
in CD4 T cell count throughout the day, while CD8 T cells and CD19+ B cells increase between 8.30 a.m.
and noon with no change between noon and afternoon. Natural Killer (NK) cell counts, on the other hand,
are constant throughout the day.(5) Circadian variations in circulating T-cell counts have been shown to
be negatively correlated with plasma cortisol concentration.(6, 7, 8) In fact, cortisol and catecholamine
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 990