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FISHERIES AND MARINE SERVICE
Translation Seiles No. 2995
Immune globulins
by Thomas TaIlberg
Original title: Immunoglobuliner
From: Finska Laekare Saellskapets liandlingar (The Finnish Medical Society Reports), 111(1) : 52-68, 1967
Translated by the Translation Bureau(LT/PNB) Multilingual Services Division
Department of the Secretary of State of Canada
Department of the Environment Fisheries and Marine Service
Halifax Laboratory Halifax, N.S.
1974
18 pages typescript
SECRÉTARIAT D'ÉTAT
BUREAU DES TRADUCTIONS
DEPARTMENT OF THE SECRETARY OF STATE
TRANSLATION BUREAU
DIVISION DES SERVICES MULTILINGUAL SERVICES CANADA
TRANSLATED FROM — TRADUCTION DE INTO — EN
Swedish English
PUBLIeHER — ÉDITEUR PAGE NUMBERS IN ORIGINAL
NUMÉROS DES PAGES DANS
L'ORIGINAL
DATE OF PUBLICATION DATE DE PUBLICATION The Serobacteriological
Institute of Helsinki Y 52 -68 ISSUE NO.
NUMÉRO VOLUME
Universit YEAR
ANNÉE PLACE OF PUBLICATION
LIEU DE PUBLICATION
NUMBER OF TYPED PAGES
NOMBRE DE PAGES
DACTYLOGRAPHIÉES 111 1967 1 Helsinki, Finland
18
DIVISION MULTILINGUES
AUTHOR — AUTEUR
Thomas Tallberg
TITLE IN ENGLISH — TITRE ANGLAIS
Immune globulins
TITLE IN FOREIGN LANGUAGE (TRANSLITERATE FOREIGN CHARACTERS) TITRE EN LANGUE ÉTRANGÈRE (TRANSCRIRE EN CARACTkRES ROMAINS)
Immunglobuliner
REFERENCE IN FOREIGN LANGUAGE (NAME OF BOOK OR PUBLICATION) IN FULL. TRANSLITERATE FOREIGN CHARACTERS.
RÉFÉRENCE EN LANGUE ÉTRANGÈRE (NOM DU LIVRE OU PUBLICATION), AU COMPLET, TRANSCRIRE EN CARACTÈRES ROMAINS.
Finska Laekare Saellskapets Handlingar
nzre:RENcE IN ENGLISH — RErinr.:NcE EN ANGLAIS
The Finnish Medical Society Reports
REQUESTING DEPARTMENT Environment TRANSLATION BUREAU NO. 784484 MINISTÈRE-CLIENT NOTRE DOSSIER N 0
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PERSON REQUESTING Allan T. Reid DEMANDÉ PAR
YOUR NUMBER VOTRE DOSSIER N 0
DATE OF REQUEST DATE DE LA DEMANDE
SOS-200-10-8 (REV. 2/68)
7030-21-029.8333
APR 2 -- 1574
MUD For infonr.:-:::k•7;
TRA DU C- N N
Informa:ion
evi •
• ' DEPARTMENT OF THE SECRETARY OF STATE
TRANSLATION BUREAU
SECRÉTARIAT D'ÉTAT
BUREAU DES TRADUCTIONS
MULTILINGUAL SERVICES
DIVISION
DIVISION DES SERVICES
MULTILINGUES
CLIENT'S NO. DEPARTMENT DIVISION/BRANCH CITY
N° DU CLIENT MINISTÉRE DIVISION/DIRECTION VILLE
Environment Fisheries Service Ottawa, Ont.
BUREAU NO. LANGUAGE TRANSLATOR (INITIALS)
N° DU BUREAU LANGUE TRADUCTEUR (INITIALES)
784484 Swedish LT 7P1-11.- APR 2 - 1t:1 74
IMMUNE GLOBULINS
by
Thomas Tallberg
The Serobacteriological Institute of Helsinki University
It is rather peculiar that within a research field as
extensive and diverse as immunology, the most important research
tool, - immune globulins, - at the same time constitutes its
perhaps most interesting object of study. The unbelievably rapid
development in this field makes it difficult even for professionals
to follow and coordinate all the new sprouts of knowledge. Ex -
tensive surveys with reference lists and detailed descriptions
are published every year. In this respect I refer to articles by
Fudenberg (5), Gitlin (6), and Fleischman (3).
It is difficult to present this group of problems in a
readily understandable form without reverting to a mere outline.
uNlupnD /
1111011T.Z. ■ i011 smuiaracnt SOS-200-10-31
7530-21-02g-5332
To be able to offer something to both -the -pxafessi.onal man and the
uninitiated, I have chosen a-type of presentation that is 1argeTy
based on tables. I believe that the-mass of details In this way-wi11
be easiertn digest.
Any strict classification of research areas within im
munology is bound to be deficient because of the striking inter-
action of the areas. However, an orientational outline (table 1)
serves a useful purpose. The interplay of the properties and effects
of immune globulins is symbolised by the two-headed arrow con -
necting the main branches of immunology : irimunochemistry, immuno-
genetics, transplantation and tumour immunology, and immunobiology.
TABLE 1
IIDiUNOLOGY
(immunopathology )(immunophysiology)
Immunochemistry mmunogenetics Transplantationand tumour
mmunobiology I1
1immunoloq:
Primary and ter- Blood group Allergy
tiary structure, serology, glob- Anaphylaxis
kinetic and phys-: ulin classiFi^ Atopy
iochemical pro- cation, serum Cell-bound
1perties ofglobulin
protein,enzyme, reaetions
etc.
Classification and structure
Autoimmunity
Antihormone
Antienzyme
Transport
protein
A complicatod pê^^_er-ij of n:Rti^od.ies h.4,% vecn, developed
(53)
since the timeg when t-jie pi©nenr-s of th,q field nzkâe tha-ir great
Ter,
Human serum in starting point
• '
• •
igA •4, IgG •
(53- 54 )
3
inventions. Tiselius and Waldenstrom, the former by means of
electrophoresis and the latter by ultracentrifugation, established
that antibodies (antibody activity) are found in the gamma globulin
fraction mainly as :7S gamma globulin, today called immune globulin
G (IgG), and in a macroglobulin fraction as 195, now called IgM.
This system was developed further by Grabarts immunoelectrophoresis
(fig. 1 A).
Cathode Anode- Antihuman gamma globulin serum
A)
B)
Figure 1. Immunoelectrophoresis with specifigama_globulin serum.
TABLE II
Immune globulin .ol ejide chains and inolecular structure
Light chains; Ig type Heavy chains Ig class (24) Structural formula
'X (kappa) Mlambda)
:y K l '(gamma) IgG or y G L !,,k(mu) IgM or 11.1
1(X(alpha) IgA or ? A & (delta) IgD or ?D 1 1
.)(2 2x2 in or V'-2112)n n=5
- 6 or (0e2/12) n n=1,2,3 ,or
62X2 °r e2/12
.
IgM IgG , or
Y Y
or X
Disulphide linkages
IgA or )■ or.
a a
or 4
i , i • Mol. % of Amount in Re- :T2* Carbon w. . total:mg/100 ml•newal days hydrate '
Ig serum g/day . in % ' . /molecule
Synonym :Sed-- I Amen- ;
I tation;
h; A/2-2SY2 , 3S V1
2%
lo%
?
Class
7S I 160000
7-163 160000- 900000
19S 1000000
78 . 160000 160000?
28, .39 ca. 15000'
.ca. 2 gr
0,2-0,7
?
IgG
IgA
Ig1■1
xeo ien Low molecular imm.globulins
yG, 78y, y Ya
•>PA, yAl, bsA
ylM, 199? • POI •
J Reagitt, allergin
70-80
8-15
• 8-15
>1
600-1600 mg
90-390 mg
70L.90 mg
0,3-40 Mg
1,0 mg
go—so
4
TABLE III
Physical properties of immune globulins
*) T2 = half-life
Research on this heterogeneity is still going on and is based on the
fact that the basic structure of the four main classes of immune
globulin, IgG, IgM, IgA, and IgD (and IgE ?)i consists of four poly-
peptide chains. A complete immune globulin molecule is composed of
two identical H (heavy) chains with a molecular weight of about
55,000, and two L (light) chains (mol.w. about 20,000) bound to-
gether with disulphide links. The chains determine which main
class of immune globulins is in question. The L chains among which
two polypeptide structures, (kappa) and (lambda), can be dis-
tinguished, are common to all main groups of antibodies, - how-
a ever, in such/way that each complete molecule contains two identical
ulight" polypeptide chains (2Xor 2)i.), as shown by table II. Tables
=and IV summarize some of the general properties of human immune
5
globulin as well as some of its most typical physical parameters.
TABLE IV
General nroperties of immune globulins
General properties
Complement fixationAgglutinationPrecipitationCrossing of placental barrierAnaphylaxis and passive cutaneous
anaphylaxis
IgG IgA Ighi IgE IgD
Genetic variants
(56)
The main classes of immune globulin show some genetically,
conditioned diffe.rences. Two different types of antigenicity can
be distinguished. One of them is relatively easy to observe, as the
antigen variants create specific antibodies in other animal.groups
if these are immunized with heterologous material. The second type
is based on much smaller variation in the antigenic structure,
probably on small differences in the amino acid sequence or in the
tertiary structure. The last mentioned variants are called allo-
types or isoantigens and can in general only be discovered within
one and the same animal group. In humans, these are called Gm
determinants and are situated mainly in the so-called Fc fragment
of the heavy chain of an IgG molecule, but certain determinants
are probably created by the combined effect of H and L chains.
Corresponding allotypes in the^/-chains of the light chain group
are named Inv determinants. It has not been possible up to now
Mew!
Jleavy I • •
1 ----=r7=-7771
•ca • • : e •
1
kO8% . "20% ''..3.%.:f4% i813 % : •-Y-qa G1 let lee :Ma** !Pie** ?
ftWe) (N.e) WI) (Gé) • . :n • • • • •
' . c :5
ig
•
Genetic Inv allotypes Curt
Isoantigenic
1
- 11
. 34%
Light 1
f • 66 %
Chains
Groups
Antigenic (A4+. A4—)* (Z1+, Z1—) subgroups
a
to group )1/4-polypeptide chains accor_cling o.thjs sy_stem
(table V).
TABLE - V
Genetically conditioned -variants of immune .globulins
Immune g1ob3.11.in vG, yD,
(57- *) (18) (15)
**) (22) -***) (10)
t) WHO has recently published e :nomenclature :listing ;the ,:about :20 allotypes.
Production and function
It seems to be necessary to :different-late ..between -the 5steges
In antibody formation lea.ding e ey.nthesis :of -.immune g b.ulin And
the fo-rmation of specificity :and ;the tertiary .strueture -of ;anti_bo.di-es.
For the time% being, the •eve.lopment -is ...being remaained 33y :-rins ;of
:58)
f
s • [sl ' ==S:=7«.f_ZZi_ 2e
• L s n . . C terminal
7
Burnett's clone selection theory according to which the antigen
stimulates a predetermined cell clone which becomes responsible
for production of a specific immune globulin with a limited varia-
bility (about 10,000). Another group of researchers havapresented a
so-called instructive theory according to which the structure and
physicochemical nature of the antigen actively affects the formation
of specificity. And finally, Grabar is of the opinion that immune
globulin constitutes a physiologicely adaptive transport mechanism.
All main theories contain both acceptable and unacceptable axioms )
a combination of which possibly lies nearest to the truth.
The classical portrait of immune globulin is a spherical
elongated molecule with a length of about 240 A and cross sections
of 19 and 57 A. The four basic chains are intertwined and held to-
gether by a number of disulphide links within a chain and between
the different chains. The molecule is bivalent which means that two
antigen molecules can be attached to it. The combining sites are
situated so that both ends of an IgG molecule are able to attract an
antigen molecule. On the other hand, the five constituents of an IgM
molecule are, for some reason, monovalent when tested individually
after fission (figs. 2, 3).
IgG
240 A
about 107 amino acids variable constant
L chain qa 'tviimteloommero c N' terminal cg;fEsizME=3
-5-5
H chain
Fc . FraweilL •
Figure 2. Heavy and light chain structure for IgG molecules, modified after Ovary_ (16). Combining site regions are marked with (X), disulphide links within chains are shown as (). The number of the latter has not yet been finally determined. The com-
8
plementary variables and constant parts of L and H chain poly - peptides are marked in different ways because they are not completely identical. Areas affected by papain and pepsin are shown. The molecule is split into main fractions (Fab)2 and Fc (see fig. 4).
101:41{,.[71 r ftroui
X X
J%----tx • (.7% ‘\..e e •
Figure 3 A. The structure of an IgM molecule is probably regulated by disulphide links which connect the five basic molecules (see fig. 2) at one of the combining regions (the variable part of an.Lor chain) of every basic unit. Thus several alternative molecules could be created. Two examples are illustrated above. Changes in the con - figuration depend on an active binding of antigens. A tightly closed palisade formation can be seen at the end of agglutination (fig. B).
. - , . • . •
...t. -
• • as : ■1/4
•
,
•
• jel --«," • .
tee' im • •,• ;t
• rs:.;r.e.:;• , • • •;;27.„1 •s: • •• .• • 1;:r."
B. Latex particles enlarged 60,000 times by electron microscopy. Immune globulin molecules have fastened in different places on the surface of the latex particle, and different agglutination phases occur: The=otein antigen conjugated with the latex particle is invisible in this enlargement. (Unpublished results, Tallberg & Weckstrem).
Light .chain (L)
Heavy chain (H) ' ' IgG-molekyl
)■
cOon COOH
Figure 4. Snlittini . of immune globulin (earlier often called Porter's Fragment).
9
Fragment Fragment ' . Fragment *. ' .. : ' Fragment Pc _ — . • (Fab). . . l'ab • ' ' • . Pd
• . papain
PePsbl . kedjor
COOÙ NH • : I' H
•
* •
II .
. . • 14 . .
. t - . .
. . • .. t . . ' . .
Gm, . .
• . •
.
. .
. . .
determinants + Splitting of disulphide links determinants ** Combining sites
Disulphide links COOH= C-terminal N112= N-terminal
The combining sites are able to bind molecules with about 9
amino acids (Kabat (14), Singer & Doolittle (20) )) mhich corresponds
to a molecular weight of 500 - 1,000. An interaction of H and L
chains is required to create a fully combining region. The binding
force is not a covalent chemical bond but is created as a consequence
of a joint effect of several weaker forces such as the van der Waals
dipole moment, hydrogen bonds, and Coulomb forces (see Abraham (1) ).
The sum of these forces seems to be relatedto the character of complem.
mentary tertiary structures in such a way that the better the com-
bining site of the immune globulin coincides with the antigen, the
firmer the bond becomes. This force, i.e., the avidity of immune
globulin, usually increases in relation to immunization time. It is
1 0
also probable that if the reaction time becomes extended, the antigen-
antibody complex undergoes an active conformational change which re-
sults in a firmer aggregate with a decreased reversibility.
One half of a light chain molecule (about 107 amino acids)
is variable, while the other half, i.e., the C-terminal part, is more
or less constant. A corresponding part of a heavy chain polypeptide
is variable as well, and this variable part constitutes the combining
region together with the corresponding part of the L chain (fig. 2) 1
(Singer (20) ).
Only five different positions of these variable polypeptide
chains display variations of the amino acid sequence (Kabat, personal
communication). As only 2 - 3 different amino acids have been dis-
covered in these variable points, the specificity of the combining
region is hardly regulated by changes in the amino acid sequence
alone. An active conformation of the volume structure of immune glob-
ulin is probably important for the specificity and action of the anti-
body.
The C-terminal part of the H chain is, like that of the L
chain, constant, with the exception of certain amino acidic differences
which form a basis for the antigenic and isoantigenic variation that
has been discovered in immune globulin classes (Ovary, 16).
This presentation of the infrastructure of immune globulins
is the joint result of efforts by several research teams. An important
part of these efforts has consisted of enzymatic decomposition and
fission of disulphide 11,nks- . The term Porter's fractionsis used here
after its inventor Porter. These fragments of the gamma globulin mole-
cule are called Fab, Fc, and Fd (fig. 4), - terms that often occur
in modern theoretical immunology. It has been discovered that
(59)
the (Fab)2 fragment alone is able to bind two antigen molecules^
while the Fc fragment (He:nneY & Stanworth (11) ) has no combining
sites. However, it binds complement (out of which about 8 components
are known today), fixes immune globulin in cells and determines
whether immune globulin can cross the placental barrier, etc.
(Table IV').
Wing, to the very effective transplacental transfer of mainly
IgG during the final stage of pregnancy, active production of immune
globulin during the fetal life is very low. However, it has been
possible to prove that a potential ability to produce immune globulin
actively exists already during the embryonic life, since the thymus,
which has an important function in regulating the defense mechanism,
is e:cistent. As for the questions of immunological specificity,
hypersensitivity, and immunotolerance, we refer to Good & Gabriels%n
(7).
The cellular phases of immune globulin production constitute (60)
a complicated chapter. We do not know enough of what actually happens
after phagocytosis with the consequent antigenic coding, the transmit-
tance of this coding (via RNA or 1ZiT:1+ the antigenic determinant ?
(Braun & Cohen (2) ), the creation of cell-mediated hypersensitivity
reactions - immunological memory carried by some lymphocytes
while the rest of them develop into complete plasma cells producing
immune globulin, - formation of the tertiary structure and specificity,
- formation of natural antibodies, etc. A plasma cell is finally
clearly able to produce one or several specific immune globulins,
although always of one type only (Igili, IgA or IgG).
12
Anew-born baby starts actively producing immune globulin,
primarily IgM (against new antigens) at the age of 4-5 weeks, and at
the age of 3 years, the child reaches a relative composition of IgM,
IgG and IgA similar to that of adults (table III), occurring in the
mentioned order. Lfter this stage has been reached, half of the body's
gamma globulin reserves usually lie in the circulating plasma while
the rest of it is found in the extravascular part of the extracellular
body fluid. However, different organs show varying concentrations.
Antigen, which constitutes the actual stimulus for the
specific immune globulin synthesis, often gives rise to both a primary
and a secondary immunareaction. In the primary phase, when the immuno-
logical memory and the "delayed hypersensitivity" are created, an
irmune globulin synthesis results mainly in IgM. This is derived from
plasmacytoid PAS-positive cells. IgA is formed as well in the tran-
sitional phase) while a noticeable IgG production takes place in the
seconctryphase (Janeway, 13). It is often characterised by a high
antibody titre. A reinfection or an immunizing "booster" (or re-
vaccination) therefore most often result in a rapid IgG titre increase.
Additionally, certain forms of antibodies occur in urine,
saliva, and colostrum, which are not fully identical wlth the four main
groups of gamma globulin present in plasma (Gitlin, 6). It muetbe re-
membered as well that all immune globulin types are not even known.
One of the problems is that a great part of human globulin consists of
immune globulins such as "natural antibodies" (like properdin),
"isoantibodies", opsonin, etc, the specificities of which have not been
determined yet.
13
Immune .ffl.obulin - deficienoy and malformation
In normal cases such a physiological balance is created
as to reF,ulateautomaticallythe amounts of immune globulin. How-
ever, this mechanism with anabolism, catabolism, and consequent half-
lives naturally displays both physiological and pathological varia-
tions.
Different forms of overproduction can be discerned,such as poly-
alonal and monoclonal gammopathies,as well as deficiencies like
common hypo- or agammaglobulinemias. The specific lack of a certain
type of immune globulin is called dysproteinemia. A lack of one or
several immune globulins is often diagnosed in connection with basic
medical examination of patients suffering from recurrent common in-
fections. Recently, both Hobbs (12) and Janeway (13) have produced
excellent and detailed descriptions of these complex antibody defi-
ciencies. In children younger than 12 months a value remaining under
100 mg/100 ml is defined as indicating hypogammaglobulinemia. In
older children this limit value is 200 mg/100 ml.
As many cases already can be clinically treated with human
gamma globulin, I have summarized in table vr the different forms
of gamma globulin deficiencies. It might be of special interest to
point out that the most difficult form of deficiency, "thymus
alymphoplasia", along with the lack of "delayed hypersensithrity",
(e.g. tuberculin reaction), is often characterized by a complete
agammaglobulinemia. The other cases are mostly only relative deficien-
cies and must therefore be defined as hypogammaglobulinemias.
Dysproteinemdas with consequent "immune paresis" display a total
14
lack of either a certain immune globulin or two classes of it.
An abnormal variation in the relative physiological combination
of the four main classes is often created in this connection.
Efforts have been made to design a numerical nomenclature for
dysproteinemia types, but unfortunately the usefulness of such a
nomenclature is impaired by extensive variability and the fact that
it does not directly reveal which type of dysproteinemia is con-
cerned.
The syndrome of immune globulin deficiencies certainly has a
very complicated etiological background. However, certain simple
theories can be conjured astp how the deficiencies are created.
A) The light chain synthesis is lacking, resulting in a shortage of all
immune globulins. B) Certain heavy chain types (p,ft.,CX, 8 ) are not
produced, which results in selective dysproteinemias. C) The amino
acid sequence of the tertiary structure of a combining site develop
defectively and decrease the effectivity of immune globulins. D)
The immune globulin molecule does not emerge from the producing cell
in an undisturbed state or is affected by humoral depressor
mechanisms, etc.
.As mentioned earlier, a group such as dysproteinemias at
least gives rise to some optimism because a great number of patients
have been saved by supporting therapies with human gamma globulin,
antibiotics, and what is perhaps most important, by effective pre-
ventive hygienic care. However, the genetic variations of immune glob-
ulins do create a difficulty mhich can cause unexpected complications.
TALLE VI
Antibody deficiency syndrome *)
A. Thymus alymphoplasia
B. Congenital a(hypo)gamma.globulinemia
C. Acquired hypoganunaglobulinemia1. Primary (idiopathic)2. Secondary
a. Radiation
b. In reticuloendothelial diseasesc. Chemical, cytotoxic (pharma-
cological) suppressiond. General protein deficiency
D. Dysganma,s ,̂lobulinemia
1. Transient
a. Neonatal dysganunaglobulinemiab. Transient hypo;amnaglobulinemiac. Transient hypoganLnagloUulinemia
2. Congenital dysgamma^lobulinersia
3. Acquired dysgammaglobulinemia
E. In connection with apparently normalimmune g,_lobulins
Farailial, fatal results before the age of 2,usually male children, "delayed hypersensitivitysr-reactions lacking.Sex-influenced recessive, most often male children,
starts at the age of 6 months-3 years, relatïvely
conma.zdeficiency syndrome, "delayed hypersensitivi-
ty" present.
At any age.Familial predisposition ?
Malabsorption, malnutrition, renal causes.
Prematurity and a so-called brief physiological. (65)In children, delayed development.In adults, complicated and diverse etiology.
Total lack of one or several immune globulintypes, IgG, IgA, Igii, IgD. In connection with e.g.
ataxia telangiectasia, the Wiscott-Aldrich syn-
drome, etc.In certain autoiimuune and infectious conditions.
*) Modified after Janeway (13a).
16
Polyclonal gammopathy, an overproduction of gamma globulin,
can be physiological and occurs in the form of a generally broad
increase in all immune globulin types. It occurs often it' bbnnettron
with cirrhosis, chronic infections, LED, hyperglobulinemic purpura,
chronic sialoadenitis and certain collagenoses, sarcoidesis, rheuma-
toid arthritis, and autoimmune conditions. As a whole., it could be
stated that even if the clinical condition is often •iIptoved by
cortisone treatment, we do not understand the etiology of it.
I shall not dwell on problems related to the "théunatoid
factor syndrome" because these have recently been dealt With by both
Squire (21) and Gothoni (8).
The actual paraproteinemias are almost exclusiVely related
to the so-called monoclonal gammopathies. Myelona can very rarely
be regarded as a result of a simultaneous aberration of several ful=
ly separate cell clones.
Following Waldenstromts discovery of nacroglobulinenlas,
cases of nyelomatosis have been found within all •itune grobulin
classes. The small monoclonal bands making their appéaYabce during
electrophoresis were named M-bands by Riva (19), and •they can be
seen in immune electrophoresis even more clearly as nodules on the
precipitation lines of respective immune globulins (fig. 1 B).
The most common form is the IgG-type of nyeloma (about 65 %
of all cases) while IgA constitutes about 25 % and IgM 1 %.
There have been a few cases of IgD myeloma as well. 1 % of the Caseà
have not been classified yet. Certain gamma globulin aberrations
make their presence known in overproduction of light chain poly-
peptide components alone. This is the cause of the Bence-Jones
17
protein in which as much as 50 g/day of certain light chain
type components are found in the urine in monomeric or dimeric
form. Consequently, one would expect to come upon cases with an ab-
normally increased heavy chain production without a corresponding
increase in light chain production. Franklin (4) has been the first
to describe such cases.
The clinical course of paraproteinemias can be rapidly pro-
gressing and extremely malign, but a surprisingly great number of
cases represent a benign or only slowly progressing disease (Hobbs
(121) ). Excluding asymptomatic cases, the ii-band is present in
1 % of normal population and 3 % of persons over 70. These essential
monoclonal gammopathies do not make our problems easier to solve.
Often the disease is revealed by classical bone lesions,
different forms of anemia, immunoparesis,(primarily in connection with
IgG myeloma), renal complications, amyloid formation, pyelonephritis.
and hypercalcemia (often in IgA myelonm), cryoglobulinemia,
and last of all IgTI myeloma with the so-called viscosity syndrome.
This means mainly a feeling of thorough fatigue, distension of
the retinal veins, frequently with bleedings in the bottom of the eye,
an SR exceeding 100, and purpura.
However, these symptoms are not limited to one parricular form of
myeloma, and Waldenstrom has discovered e.g. that because of different
polymerization phenomena, certain forms of IgG myeloma and the Bence-
Jones protein lead to results strongly resembling the symptoms of an
IgM myeloma.
(67)
19. Riva,
• 18
The data concerning immune globulinsaxe accumulating mith such
a speed that we shall probably soon find ourselves in a situation
where we do no longer control the problem. We are conscious
of the fact that immune globulins are living proteins with all the
relevant details that are so fascinatingly difficult to understand.
The usability and the advanced specificity by mhich gamma globulins
are characterized make us grateful for the Privilege of being allowed
to study them.
1. Amun.tra, E. P.: I •Ge_neral Path .°logy III. Ed.» editor Florey, Lloyd-! Luke LTD. (London). 1962. - 2. BRAUN, W. & CORES, E. P.: On the Role of ! . -nucleic Acids in Antibody Formation. Information Exchange Group No. 5, •
• Irumunopathology, Memo 1966. - 3. FLEISC_IIMAN, J. B.: Ann. Rev. Biochem. 1966:36:11. 4. FrIANKLIN, E. C.: J. Exptl. Med. 1964:120:691. 5.1et, 33EN-
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