Download Agammaglobulinemia and Hypogamma- globulinemia

Agammaglobulinemia and Hypogammaglobulinemia-Relationship
to the
Mesenchymal Diseases*
ROBERT
A. GOOD
AND
(Presented
ANN
E. GABRIELSENt
by Dr. Good)
From the Pediatr~c Re.search L.aboratories of the Varieu) Club Heart Hospital,
Unioereiuj of j]i[mnesota, Minneapolis, Minnesota
In beginning this discussion of the relationship of agammao'lobulinemiahypogammaglo?ulinemia
to the mesenchymal or "collagen" ~1"OUpof disea 'es, I would like to set the minds of some of the investigators at ease. We
hav~ not observed, nor do we know of others who have observed, patients
having any of .the extreme immunologic deficiency diseases together with
acute .r~e~matlC fever. However, Gitlin (22) has seen a form of glomerulonephritis 111two patients with agammaglobulinemia
which he will mention 111the Discuss.ion. Thus, it seems that at least one form of presumed
post~treptococcal
disease can occur in patients with extreme immunologic
deficiency.
Interes~ in the ,simultaneous occurrence of mesenchymal disease and se".ere deficiency of ,gamma globulin developed soon after Bruton's (9) clas~lCal d.escnptIOl1 of agammaglobulinemia.
In the early reports, a number of
111Ve~tlgators documented the observation that joint swelling, redness and
effusion had occUlT~d in agammaglobulinemic
patients under study (11,
36, 44). In several mstances, although septic arthritis was suspected, no
* ?riginal studies discussed were supported by grants from the U. S. Public Health
Serv:,ce, the N ational Foundation, the Minnesota Chapter of the Arthritis and Rheurnatism Foundation and the American and 'linnesota Heart Associations.
. t Department o.f Pediatrics, Training Grant HTS-5462, 1 ational Institutes of
Health, U. S. PublIc Health Service.
368
Hlld I~KILlnll1ltKI()I)UIIlI
.nua came rrom 'JlI.l: 1)():i~()11 1:'>""'1 1\;" ".r ''''''''''''',1
Hlld :il,lill (.12). Tiley presented these ca 'cs Ull IeI' tile heading or "(,CIIOHYII()viLiH";however, ill several instance the case histories were most sugW'HLiv(lor rheumatoid arthritis. A short time later, we (32) presented Our
(lXP )l'iCI1CCwith
cvoral agammaglobulinemic
patients who had perfectly
Lypical manifestations
of rheumatoid arthritis. It was our contention at
(,Iml, Lime, strongly reinforced by subsequent experience, that a disease
illdiHLillgui,'ilable clinically from rheumatoid
arthritis occurs with inordiuuto frequency among: both children and adults with agammaglobulincmia. l3al'andUIl et al. (3), too, have observed a striking frequency of
join] lisca c among patients with "Aiuikorpermomqeleundrom,"
but, beGIWHO of the mild nature of the disease observed,
have chosen to refer to it
ItH toxic arthritis rather than as true rheumatoid arthritis.
Before pre enting case material supporting our contention that several
mOHCIl.hyrnal diseases are intimately
related to the immunologic defieicil 'y di orders, it seems appropriate
to present a classification of the
Iorrns
f agammaglobulinemia-hypogammaglobulinemia
as we now see
(,JtCI ,a' well as a description of the nature of the dysproteinemia
and the
immunologic defect in each instance. The nature and extent of the immunologi deficiency seem to be of central importance in a discussion of relationship: of the mesenchymal and immunologic deficiency diseases.
Durinz the 10 years since Bruton first described the disease he called
agammaglobulinemia,
approximately
350 cases have been reported in the
lit rature (reviewed in (31)), and a number of medical groups in several
I arts of the world have had extensive experience with large groups of these
patients, Although there are minor differences in the proposed classifications, as well as in experience and interpretation,
the parallels in the findings in these large and well studied groups of patients have been striking.
The classification of the members of our group of agammaglobulinemiahypogammaglobulinemia
patients is set down in table 15-1. As we gain
understanding
of the mechanisms involved in these defects, and as our
experience grows, new groups will have to be added and the designations
of the old groups changed. To us, classifications are not right or wrong, but
useful or not useful; and the classification here set down has been useful up
to the present. The table includes the number of patients in each category
studied at the University of Minnesota.
The evidence that one form of congenital agammaglobulinemia
is inherited as a simple Ifendelian recessive trait is substantial. Kulneff ei al.
(44) first presented substantial evidence of the genetic nature of childhood