Immunoglobulin G Deficiency

Background
Immunodeficiency diseases are commonly
classified into disorders that affect one or more of
the 4 major limbs of the immune system. These
limbs are (1) B cells, ie, humoral immunity; (2) T
cells, ie, cell-mediated immunity; (3) phagocytes;
and (4) complement.

B-cell immunity is mediated by the
immunoglobulins and is commonly referred to as
humoral immunity. Humoral immunity is
differentiated from T-cell immunity, which is
commonly referred to as cellular immunity, and
from phagocytic cell immune function.
Immunoglobulins, which are protein molecules that
contain antibody activity, are produced by the
terminal cells of B-cell differentiation known as
plasma cells. Immunoglobulins have important
roles in humoral immunity, and they consist of 5
major classes or isotypes: immunoglobulin G
(IgG), immunoglobulin A (IgA), immunoglobulin
M (IgM), immunoglobulin D (IgD), and
immunoglobulin E (IgE). The most abundant class
of immunoglobulins in the blood is IgG (73%),
which has a molecular weight of 150 kd. IgG is
present in plasma and external secretions and is
expressed on the B-cell membrane.

IgG is further subdivided into 4 subclasses: IgG1,
IgG2, IgG3, and IgG4. Fortunately, for ease of
recall, the serum concentrations of the subclasses
directly correlate with their numerical
nomenclature, such that IgG1 is found in greater
concentrations than IgG2, and so forth.

In 1952, Bruton described classic X-linked
agammaglobulinemia due to B-cell deficiency in an
8-year-old boy. The child presented with frequent
pyogenic infections, repeated episodes of sepsis
with the same serotypes of pneumococcus, and
multiple episodes of mumps, yet he had no
antibodies against these pathogens. Serum protein
electrophoresis had just become available, and it
revealed that the g fraction was missing from the
childs blood.. Subsequently, patients were
described who had detectable lymphoid tissue and
B-cells but had decreased IgG levels and/or lacked
specific antibodies. These conditions are now
recognized as fitting the categories of hyper-IgM
Imunoglobulina G Deficitul

Fundal
Boli imunodeficitare sunt de obicei clasificate n
tulburri care afecteaz una sau mai multe din cele
4 membrelor majore ale sistemului imunitar.
Aceste membrele sunt (1) celule B, adic
imunitatea, umorale; (2) celule T, i anume,
imunitatea mediat celular; (3) fagocitelor i (4) se
completeaz.

B-celule imunitatea este mediat de
imunoglobuline i este denumit n mod obinuit ca
imunitatea umorala. Imunitatea umorala este
difereniat de imunitate de celule T, care este
denumit n mod obinuit ca imunitatea celulara, si
din functia de celule fagocitare imunitar.
Imunoglobulinele, care sunt molecule de proteine
care conin activitate anticorpi, sunt produse de
celulele terminale de difereniere a celulelor B
cunoscut ca celulele plasmatice. Imunoglobulinele
au un rol important n imunitatea umoral, iar
acestea constau n 5 clase majore sau isotypes:
imunoglobulina G (IgG), imunoglobulin A (IgA),
imunoglobulina M (IgM), imunoglobulina D (IgD),
i imunoglobulina E (IgE). Clasa cea mai
abundent de imunoglobuline n snge este IgG
(73%), care are o greutate molecular de 150 kd.
IgG este prezent n plasm i secreiile externe i
este exprimat pe membrana celulelor-B.

IgG este n continuare mprit n 4 subclase:
IgG1, IgG2, IgG3 i IgG4. Din fericire, pentru
uurina de retragere, concentraiile serice ale
subclaselor corelat direct cu nomenclatura lor
numeric, astfel nct IgG1 se gsete n
concentraii mai mari de IgG2, i aa mai departe.

n 1952, Bruton descris clasic agamaglobulinemie
X-linked din cauza deficitului de B-celule ntr-un
biat de 8 ani. Copilul a prezentat cu infecii
frecvente piogenice, episoade repetate de sepsis cu
aceleai serotipuri de pneumococ, i mai multe
episoade de oreion, dar el nu a avut anticorpi
mpotriva acestor patogeni. Electroforeza
proteinelor serice a devenit doar disponibil, i a
dezvluit c fraciunea g lipsea din sangele
copilului .. Ulterior, pacienii au fost descrise care
au avut tesutului limfoid detectabil i B-celule, dar
au sczut IgG i / sau nu aveau anticorpi specifici.
Aceste condiii sunt acum recunoscute ca montarea
syndromes and common variable
immunodeficiency (CVID).

In the early 1960s, following the discovery of the
IgG subclasses, certain associations were also
recognized between individual subclass
deficiencies, decreased ability to respond to certain
types of antigens (ie, bacterial polysaccharides),
and recurrent infection. IgG deficiencies may occur
as isolated deficiencies (eg, selective IgG
deficiency) or in association with deficiencies of
other immunoglobulin types. Moreover, even if the
total IgG concentration is normal, deficiencies of
one or more individual IgG subclasses, significant
decreases in specific IgG antibodies, or both may
be observed.

For information on deficiencies of other
immunoglobulin types, see the Medscape
Reference articles IgA Deficiency, IgD Deficiency,
and IgM Deficiency.

Pathophysiology
B and T cells are responsible for specific immunity,
otherwise known as adaptive immunity. Adaptive
immune responses require rearrangement of the
genes responsible for the specific recognition
structures, ie, immunoglobulins for humoral
immunity and T-cell receptors for cellular
immunity. Inability to form these recognition
structures or blocks in the differentiation and
development of either of these cell types results in
primary immune deficiency. Abnormal production
of these cells may also be observed in clinical
states in which production of abnormal cell types is
pathologically excessive (eg, lymphoproliferative
diseases such as lymphoma and leukemia) or in
immunodeficiency disorders in which production is
aberrantly low.[1] Humoral immune defects can
also result from excessive loss of antibody proteins
(eg, protein-losing enteropathy, certain forms of
nephritis), even though the B-cell mass may be
normal in those conditions.

IgG is well distributed in intravascular and
extravascular spaces and is important in the
secondary antibody responses (immune memory).
It plays an important role in host defense against
infection. IgG protects tissues from bacteria,
viruses, and toxins. Different subclasses of IgG
neutralize bacterial toxins, activate complement,
categoriile de sindroame hiper-IgM i
imunodeficien variabil comun (CVID).

La nceputul anilor 1960, ca urmare a descoperirii
de subclase IgG, anumite asociaii au fost, de
asemenea, recunoscute ntre deficienele
individuale subclasa, a scazut capacitatea de a
rspunde la anumite tipuri de antigene (de exemplu,
polizaharide, bacteriene), i infecii recurente.
Deficiene IgG pot aprea ca deficienele izolate
(de exemplu, deficit selectiv de IgG) sau n
asociere cu deficiene ale altor tipuri de
imunoglobuline. Mai mult dect att, chiar dac
concentraia total IgG este normal, deficiene ale
unuia sau mai multor subclase IgG individuale,
scderi semnificative ale anticorpilor specifici IgG,
sau ambele pot fi observate.

Pentru informaii cu privire la deficienele de alte
tipuri de imunoglobulin, a se vedea de referin
Medscape articole IgA, deficit de IgD, i deficit de
IgM.

Fiziopatologie
Celulele B i T sunt responsabile de imunitate
specific, altfel cunoscut sub numele de imunitate
adaptativ. Raspunsurile imunitar adaptativ necesit
rearanjare a genelor responsabile de structurile
specifice de recunoatere, de exemplu,
imunoglobuline de imunitate umoral si T-receptori
celulari pentru imunitatea celular. Incapacitatea de
a forma aceste structuri recunoaterea sau blocuri
n diferenierea i dezvoltarea de oricare dintre
aceste tipuri de celule rezultate in deficit imun
primar. Productie anormala a acestor celule pot fi
de asemenea observate in statele clinice n care
producia de tipuri de celule anormale este
patologic excesive (de exemplu, boli
limfoproliferative cum ar fi limfom si leucemie)
sau n tulburri de imunodeficien n care
producia este aberant redus. [1] defecte imun
umoral poate duce, de asemenea, la pierderea
excesiva de proteine de anticorpi (de exemplu,
proteine-enteropatie cu pierdere, anumite forme de
nefrite), chiar dac mass-celule B pot fi normale n
aceste condiii.

IgG este bine distribuit n spaiile intravascular i
extravascular i este important n rspunsurile
secundari de anticorpi (memorie imun). Acesta
joac un rol important n aprarea gazdei mpotriva
and enhance phagocytosis by opsonization.[2]

Importantly, note that a low IgG level, with normal
IgA and IgM levels, does not necessarily equate
with antibody deficiency. The evaluation of
specific antibody responses is essential for the
diagnosis and for appropriate treatment.

For ease of discussion, IgG deficiencies may be
divided into 2 categories. The first is selective IgG
deficiency, which consists of an isolated deficiency
of IgG with normal levels of IgA, IgM, IgD, and
IgE. The second is a deficiency of IgG
accompanied by inadequate levels of other
immunoglobulin isotypes. This may occur in
various conditions, including X-linked
agammaglobulinemia (X-LA), common variable
immunodeficiency (CVID), and hyper-IgM
syndromes.

These disorders occur in persons of any age or sex.
Selective immunoglobulin deficiencies were
previously referred to as late-onset
agammaglobulinemia, and now they are classified
under the general designation of antibody
deficiency. Both pediatric and adult populations
may be affected by specific or selective antibody
deficiencies, CVID, or both. See Common variable
immunodeficiency for more details.

IgA deficiency is the most common immune
deficiency. Although some "normal" blood donors
may be found to be deficient in IgA, approximately
20% of patients who lack IgA are also deficient in
IgG2 and IgG4. These individuals appear to have a
greater risk of infection than patients with isolated
IgA deficiency.

Epidemiology
Frequency
United States
Although the frequency of isolated IgG deficiency
is not known with certainty, deficiencies in specific
IgG antibody or IgG subclass is probably more
common and occurs in families with common
variable immunodeficiency (CVID). Some reports
indicate that the prevalence of IgG deficiency may
be 1 case per 10,000 persons.

Mortality/Morbidity
Early diagnosis and treatment of IgG deficiency is
infeciilor. IgG protejeaza tesuturile de la bacterii,
virusuri, i toxine. Diferite subclase de IgG
neutralizeaz toxinele bacteriene, activeaz
complementul, i de a spori fagocitoza opsonizarea.
[2]

Important, reinei c un nivel sczut IgG, cu
normal IgA si IgM niveluri, nu echivaleaz
neaprat cu deficit de anticorpi. Evaluarea
rspunsuri specifice ale anticorpilor este esenial
pentru diagnostic i tratament corespunztor.

Pentru uurina de discuii, deficiene IgG pot fi
mprite n dou categorii. Primul este deficit
selectiv de IgG, care const dintr-un deficit izolat
de IgG cu nivele normale de IgA, IgM, IgD, i IgE.
Al doilea este un deficit de IgG nsoit de niveluri
inadecvate de alte izotipuri imunoglobuline. Acest
lucru poate s apar n diferite condiii, inclusiv
agamaglobulinemia X-legat (X-LA),
imunodeficien variabil comun (CVID), i
sindroame hiper-IgM.

Aceste tulburri apar la persoanele de orice varsta
sau sex. Deficiene de imunoglobuline selective
anterior au fost menionate ca agamaglobulinemie
cu debut tardiv, iar acum ele sunt clasificate sub
denumirea general de deficit de anticorpi.
Populaii att copii i aduli pot fi afectate de
deficiene specifice sau selectiv de anticorpi,
CVID, sau ambele. Vezi imunodeficiene comune
variabile pentru mai multe detalii.

Deficit de IgA este deficit imunitar cele mai
comune. Dei unii donatori de snge "normale"
poate fi gsit pentru a fi n deficit de IgA,
aproximativ 20% dintre pacientii care nu dispun de
IgA sunt, de asemenea, deficit de IgG2 i IgG4.
Aceste persoane par a avea un risc mai mare de
infectare dect pacienii cu deficit izolat de IgA.

Epidemiologie
Frecven
Statele Unite
Cu toate c frecvena de deficit izolat IgG nu este
cunoscut cu certitudine, deficiene n special IgG
sau IgG subclasa este probabil mult mai comuna si
apare in familiile cu imunodeficien variabil
comun (CVID). Unele rapoarte indica faptul ca
prevalenta deficit de IgG poate fi un caz la 10.000
de persoane.
essential to prevent and control both morbidity and
mortality.
IgG subclass levels are highly variable, even within
individuals at different points in time. Their
development in early childhood varies from
subclass to subclass; IgG 2 is the slowest to reach
adult values. Additional deficiencies may become
apparent because of defective switching between
different IgG subclasses.
Sex
Males and females are affected.
Age
Both children and adults are affected. Children
younger than 24 months cannot make much IgG2;
hence, measuring the IgG2 subclass concentration
before this age is not meaningful.

The most common subclass deficiency in early
childhood is IgG2 deficiency; in adults, IgG1 and
IgG3 deficiencies predominate. IgG1 accounts for a
higher proportion of the total IgG in children as
compared to adults. Although children rapidly
attain adult levels of IgG1 and IgG3, the
development of IgG2 and IgG4 is slower. In some
children, maturation of the full range of IgG
subclasses may be delayed until the teenage years

One recent study found an isolated IgG3 subclass
deficiency was the most common IgG subclass
deficiency in Thai children. IgG3 subclass
deficiency, either isolated or combined with other
IgG subclass deficiency, was found in 85.5% of 55
children, most of whom were first evaluated for
recurrent sinusitis.[3]


Mortalitatea / Morbiditatea
Diagnosticul precoce i tratamentul deficitului de
IgG este esenial pentru a preveni i controla att
morbiditate i mortalitate.
Nivelurile de subclasa IgG sunt foarte variabile,
chiar i n indivizi la diferite momente de timp.
Dezvoltarea lor n copilria timpurie variaz de la
subclasa la subclasa, IgG 2 este cel mai lent pentru
a ajunge la valorile de la aduli. Deficiene
suplimentare poate deveni evident din cauza
comutare defecte ntre diferite subclase IgG.
Sex
Brbaii i femeile sunt afectate.
Vrst
Att copiii, ct i adulii sunt afectai. Copiii mai
mici de 24 de luni nu se poate face mult IgG2, prin
urmare, msurarea concentraiei subclasa IgG2
nainte de aceast vrst nu este semnificativ.

Cel mai frecvent deficit de subclas n copilria
timpurie este IgG2 deficit, la adulti, IgG1 i IgG3
deficiene predomin. IgG1 reprezint o proporie
mai mare din totalul IgG la copii fa de aduli.
Dei copiii ating rapid niveluri adulte ale IgG1 i
IgG3, dezvoltarea de IgG2 i IgG4 este mai lent. La
unii copii, maturizarea gam complet de subclase
IgG poate fi amnat pn n anii adolescenei

Un studiu recent a constatat un deficit izolat IgG3
subclas a fost cel mai frecvent deficit de subclas
IgG la copii Thai. IgG3 deficit de subclasa, fie
izolat sau n combinaie cu alte deficiene subclas
IgG, a fost gasit in 85,5% din 55 de copii, dintre
care majoritatea au fost mai nti evaluate pentru
sinuzita recurent. [3]