Immunoglobulin M Deficiency

Background
Selective immunoglobulin M (SIgM) deficiency is
a rare form of dysgammaglobulinemia
characterized by an isolated low level of serum
immunoglobulin M (IgM). Reported IgM
concentrations in SIgM deficiency vary from 40
mg/dL (though some sources say 20 mg/dL) to
undetectable levels (reference range 45-150 mg/dL
in adults).[1] Recent series report IgM levels of
29.78.7 mg/dL (meanSD) for adults and
16.513.8 (meanSD) in children.[2, 3] In this
context, remember that 2.1% of "normal"
individuals have values < 2 SD below the mean and
that values in children must be compared with
reference range values for age.[4] The levels of
other immunoglobulin classes are within reference
ranges.

SIgM deficiency may occur as a primary or
secondary condition. Secondary SIgM deficiency is
much more common than primary SIgM deficiency
and may be seen in association with malignancy,
autoimmune disease, gastrointestinal disease, and
immunosuppressive treatment.

Some patients are asymptomatic, whereas others
(often infants and small children) develop serious
infections. Patients may develop prolonged or life-
threatening infections caused by both encapsulated
bacteria and viruses, especially in infancy. In older
children and adults, SIgM deficiency is usually
discovered during the investigation of other
conditions, such as autoimmune disease or
malignancy.

Serum immunoglobulin levels are controlled by
intricate immunological regulatory mechanisms,
and heterogeneity is believed to exist in the
pathogenesis of SIgM deficiency. Little is known
about the pathological features of SIgM deficiency
at a cellular level, given that the condition is so
uncommon. Processes that control the survival of
IgM in the circulation and may otherwise regulate
its concentration in serum have not been well
described; alterations in clearance mechanisms, in
addition to altered production of IgM by
lymphocytes, may contribute to selective
deficiency of this immunoglobulin isotype.

Imunoglobulina M Deficitul

Fundal
Imunoglobuline M deficit selectiv (Sigm) este o
form rar de disgamaglobulinemie caracterizat de
un nivel sczut al izolat M imunoglobuline serice
(IgM). Concentraiile IgM raportate n deficit Sigm
variaz de la 40 mg / dL (dei unele surse spun 20
mg / dl) la niveluri nedetectabile (interval de
referinta 45-150 mg / dl la adulti) [1] seria recent
raport niveluri IgM de 29,7 8,7. mg / dL (medie
DS) pentru aduli i de 16,5 13,8 (medie DS) la
copii. [2, 3] n acest context, amintii-v c 2,1%
dintre persoanele "normale" au valori <2 DS sub
valoarea medie i care Valorile la copii trebuie s
fie comparate cu valorile de domeniul de referin
pentru vrst. [4] Nivelurile de alte clase de
imunoglobuline sunt n intervale de referin.

Deficit Sigm poate s apar ca o condiie primar
sau secundar. Deficit Sigm secundar este mult mai
frecvent decat deficit Sigm primar i poate fi vzut
n asociere cu boli maligne, boli autoimune, boli
gastro-intestinale, precum i tratament
imunosupresor.

Unii pacieni sunt asimptomatice, n timp ce altele
(de multe ori sugari i copii mici) dezvolta infectii
grave. Pacientii pot dezvolta infecii prelungite sau
pun n pericol viaa att de bacterii ncapsulate i
virui, mai ales in copilarie. La copiii mai mari si
adulti, deficit Sigm este, de obicei descoperit n
timpul anchetei de alte condiii, cum ar fi boli
autoimune sau afeciuni maligne.

Nivelului de imunoglobulina serice sunt controlate
prin mecanisme de reglementare complicate
imunologice, i eterogenitate se crede c exist n
patogeneza deficit Sigm. Putin se stie despre
caracteristicile patologice de deficit Sigm la un
nivel celular, avnd n vedere c starea este att de
neobinuit. Procesele care controleaz
supravieuirea IgM n circulaie i poate reglementa
altfel concentraia acestuia n ser nu au fost bine
descrise; alterarea mecanismului de acordare, n
plus fa de producerea de IgM alterat de
limfocite, pot contribui la un deficit selectiv al
acestui izotip imunoglobulin.

Fiziopatologie
Cauza deficitului Sigm este necunoscut. Activitatea
Pathophysiology
The cause of SIgM deficiency is unknown.
Increased regulatory T-cell activity specific for
IgM has been described.[5] The absence of IgM in
the presence of normal levels of immunoglobulin G
(IgG) and immunoglobulin A (IgA) has yet to be
explained, as this appears to contradict the theory
of sequential immunoglobulin gene rearrangement.
Normal mature B cells are expected to have IgM
and immunoglobulin D (IgD) on their surfaces,
and, with proper stimulation, rearrange their
immunoglobulin genes to switch from expressing
IgM to IgG, IgA, or immunoglobulin E (IgE).

Having normal levels of IgG and IgA in the face of
low IgM is thus counterintuitive. One could
speculate that failure to regenerate B-cell
precursors could lead first to depletion of IgM, with
gradual loss of IgG and other isotypes occurring
later as class-switched memory B-cells and plasma
cells fail to be replaced. This hypothesis has not
been tested, and few studies are available to
determine whether only the serum IgM level is low
or whether the number of B cells with surface IgM
is also decreased in patients with selective IgM
deficiency. Gradually, current state-of-the-art
laboratory technology is being applied in studying
patients with SIgM deficiency, though much
remains to be learned.

The currently available literature suggests a
heterogeneous population of patients of SIgM
deficiency. Some patients are capable of normal
antibody responses of other immunoglobulin
classes following specific immunization, whereas
others respond poorly. Certain patients with
decreased helper T-cell activity have been
described.[6] Cell-mediated immunity appears to
be intact, but an insufficient number of detailed
studies are available to confirm this. Suggested
etiologies include rapid isotype switching of B cells
from production of IgM to production of other
isotypes and hypercatabolism of IgM.

Epidemiology
Frequency
United States
In a retrospective study of a large allergy practice
(20,000 patients) database, Goldstein et al reported
prevalences of SIgM deficiency of 0.26% among
adults and 0.03% among children.[2, 3]
celulelor T de reglementare a crescut specific
pentru IgM a fost descris. [5] absena IgM n
prezena unor niveluri normale de imunoglobulina
G (IgG) i imunoglobulin A (IgA) nu a fost nc
explicate, deoarece aceasta pare s contrazic teoria
secvenial imunoglobuline rearanjare genei.
Normal celulele B mature sunt de ateptat s aib
IgM i imunoglobuline D (IgD) pe suprafata lor, i,
cu stimularea adecvat, rearanja genele lor
imunoglobuline pentru a trece de la exprimarea
IgM la IgG, IgA sau imunoglobulina E (IgE).

Avnd niveluri normale de IgG i IgA n faa IgM
sczut este astfel contraintuitiv. Se poate specula c
eecul de a regenera precursori de celule B, ar
putea duce n primul rnd la epuizarea IgM, cu
pierderea treptat a IgG i alte isotypes care apar
mai trziu n calitate de memorie de clas comutate
B-si celulele plasmatice nu reuesc s fie nlocuit.
Aceast ipotez nu a fost testat, i puine studii sunt
disponibile pentru a stabili dac numai nivelul IgM
seric este sczut sau dac numrul de celule B cu
IgM suprafa este, de asemenea, a sczut la
pacienii cu deficit de IgM selectiv. Treptat, actuala
tehnologie de laborator de stat-of-the-art este
aplicat la studierea pacienii cu deficit Sigm, dei
mai rmn multe de nvat.

Literatura de specialitate disponibile n prezent
sugereaz o populaie heterogen de pacieni cu
deficit Sigm. Unii pacieni sunt capabile de
rspunsuri normale de anticorpi de alte clase de
imunoglobuline dup imunizare specific, n timp
ce altele rspund slab. Anumite pacienii cu
scderea activitii celulelor T helper au fost
descrise. [6] imunitate mediat celular pare s fie
intact, dar un numr insuficient de studii detaliate
sunt disponibile pentru a confirma aceasta.
Etiologii recomandate includ izotipului rapid de
comutare de celule B, de la producerea de IgM la
producia de alte isotypes i hypercatabolism de
IgM.

Epidemiologie
Frecven
Statele Unite
ntr-un studiu retrospectiv a unei practici alergie
mare (20.000 de pacienti) de baze de date,
Goldstein i colab au raportat prevalene de deficit
Sigm de 0,26% n rndul adulilor i 0,03% n
rndul copiilor. [2, 3]

International
SIgM deficiency is rare, with an incidence of less
than 0.03% in the general population and 1% in
hospitalized patients.[7]

Mortality/Morbidity
Since IgM may have a different range of
specificities than placentally-transferred maternal
IgG, infants can succumb to overwhelming
infections such as meningitis, pneumonia, and
gram-negative sepsis.

Patients with SIgM deficiency are susceptible to
recurrent sepsis and overwhelming infection with
encapsulated bacteria (eg, Streptococcus
pneumoniae, Neisseria meningitidis, Haemophilus
influenzae).[8, 9, 10] They may also have
autoimmune disease including glomerulonephritis
and osteomyelitis from which organisms are not
recoverable,[11, 12] as well as malignancies,
chronic dermatitis, diarrhea, and upper respiratory
infections.

Race
The incidence of SIgM deficiency in various races
has not been reported, given the low overall
incidence.

Sex
The disorder occurs in both males and females,
with no known discrepancies between the sexes.

Age
Infants can present with severe and overwhelming
infections. Older children may present with
recurrent sinopulmonary infections secondary to
encapsulated organisms and an increased incidence
of gram-negative septicemia.

Internaional
Deficit Sigm este rar, cu o inciden mai mic de
0,03% n populaia general i 1% la pacientii
spitalizati. [7]

Mortalitatea / Morbiditatea
Deoarece IgM poate avea o gam diferit de
specificul de placentally-transferate IgG matern,
copiii pot ceda la infecii copleitoare, cum ar fi
meningita, pneumonie, i sepsis gram-negativ.

Pacienii cu deficit de Sigm sunt sensibile la sepsis
recurente i infecia copleitoare cu bacterii
ncapsulate (de exemplu, Streptococcus
pneumoniae, Neisseria meningitidis, Haemophilus
influenzae). [8, 9, 10] Ele pot avea, de asemenea,
boli autoimune, inclusiv glomerulonefrita i
osteomielita din care organismele nu sunt
recuperabile, [11, 12], precum i maligne, dermatita
cronica, diaree, si infectii respiratorii superioare.

Ras
Incidenta de deficit Sigm n diferite rase nu au fost
raportate, avnd n vedere impactul general sczut.

Sex
Tulburarea apare in ambele barbati si femei, fr
discrepane cunoscute ntre sexe.

Vrst
Sugarii pot prezenta cu infecii grave i
copleitoare. Copiii mai mari pot prezenta cu
infectii recurente sinopulmonary secundare pentru
organismele incapsulate si o incidenta crescuta a
septicemiei gram-negativ.