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•Chan TM, Chan KW. Fibrillary glomerulonephritis
in siblings. Am J Kidney Dis 1998 May;31(5):E4. Department
of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong.
dtmchan@hkucc.hku.hk
Fibrillary/immunotactoid glomerulopathy is characterized by
organized glomerular deposition of extracellular,
nonbranching, immunoglobulin-derived microfibrils, which is
not associated with systemic diseases such as amyloidosis,
cryoglobulinemia, or monoclonal gammopathy. This is an
uncommon condition with an obscure etiology and accounts for
approximately 1% of primary glomerular diseases in white
populations. We report the first case of familial
fibrillary/immunotactoid glomerulopathy affecting a brother
and a sister in a Chinese family. Both patients presented
with heavy proteinuria, which improved transiently on
treatment with prednisolone and cyclophosphamide. Human
lymphocyte antigen typing for the siblings showed no
haplotype association. Despite the generally poor renal
prognosis reported in the literature, with 50% of patients
reaching end-stage renal failure within 2 to 4 years, both
patients had relative preservation of renal function
(creatinine clearance from 79 to 76 mL/min/1.73 m2 after 2
years in one patient and from 111 to 99 mL/min/1.73 m2 after
3 years in the other). Our observations show that
fibrillary/immunotactoid glomerulopathy can present as a
familial condition. Compared with sporadic cases, patients
with familial fibrillary/immunotactoid glomerulopathy may
have a more favorable renal prognosis.
•Duwaji MS, Shemin DG, Medeiros LJ, Esparza AR:
Proliferative glomerulonephritis with unusual, organized,
cylindrical deposits associated with angioimmunoblastic
lymphadenopathy-like T-cell lymphoma. Arch Pathol Lab Med
1995 Apr;119(4):377-80. Department of Pathology, Rhode
Island Hospital, Providence 02903, USA.
We describe an elderly man who developed angioimmunoblastic
lymphadenopathy-like T-cell lymphoma, followed by acute
renal failure 2 months later. Renal biopsy revealed
proliferative glomerulonephritis, which was characterized by
enlarged glomeruli with increased cellularity, thickened
capillaries, intracapillary inflammatory cells, focal
necrosis, and fibrin extravasation. Immunofluorescence
studies revealed capillary and mesangial deposits of IgG,
IgM, IgA, Ig kappa, Ig lambda, and C3. Electron microscopy
revealed unusual, organized, electron-dense deposits in the
capillary walls and mesangium. The deposits occurred as
accumulations of large rigid tubules or cylinders, which, in
longitudinal section, were double-walled. In transverse
section, the deposits were annular or horseshoe shaped and
occasionally had a central filament. The morphologic
characteristics of these deposits are different from those
seen in cryoglobulinemia or fibrillary and immunotactoid
glomerulopathies. The significance of these deposits is
uncertain; they may represent a cryoglobulin or an abnormal
serum protein related to angioimmunoblastic
lymphadenopathy-like T-cell lymphoma. The findings in this
case expand the morphologic spectrum of glomerular lesions
that may be associated with malignant lymphoproliferative
disorders and, particularly, angioimmunoblastic
lymphadenopathy-like T-cell lymphoma.
•Ferrario F, Schiaffino E, Boeri R: Fibrillary
and immunotactoid glomerulopathies. Ren Fail 1998
Nov;20(6):801-8. Renal Immunopathology Center, San
Carlo Borromeo Hospital, Milan, Italy.
Franco.Ferrario@oscb.sined.net
There is sufficient clinical and morphological evidence to
suggest that Fibrillary Glomerulonephritis (FGN) and
Immunotactoid (IT) Glomerulopathy are two different
diseases. Is still open to debate if IT glomerulopathy is a
distinct entity or is strictly associated with a spectrum of
systemic syndromes ("forme fruste" of Cryoglobulin and
paraprotein associated diseases). Further studies about
pathogenetic mechanisms of fibril or microtubule formation
may allow a better understanding.
•Ferluga D, Hvala A, Vizjak A, Koselj-Kajtna M,
Mihelic-Brcic M: Immunotactoid glomerulopathy with unusually
thick extracellular microtubules and nodular
glomerulosclerosis in a diabetic patient. Pathol Res Pract
1995 Jul;191(6):585-96. Institute of Pathology, Medical
Faculty, University of Ljubljana, Slovenia.
It has recently been suggested that immunotactoid
glomerulopathy be separated from much more common fibrillary
glomerulonephritis by ultrastructural features of highly
organized immune deposits containing tubules of more than 30
nm in diameter. We report and discuss the results of a
light, immunofluorescence and electron microscopic study of
a needle renal biopsy from a 75-year-old, non-insulin
dependant diabetic female presented with nephrotic syndrome,
hypertension and a progressive renal failure. A unique
coexistence of nodular glomerulosclerosis, as traditionally
ascribed to diabetes with a peculiar type of immunotactoid
glomerulopathy was confirmed by the exclusion of
amyloidosis, monoclonal gammopathies, systemic autoimmune
diseases and cryoglobulinemia. Mesangial, scattered
subepithelial and segmentally prominent subendothelial
immune deposits were found highly organized in mostly
parallel arrays of 40 to 91 nm thick tubules. The average
thickness of 67 nm exceeds the average diameter of tubules
in all other 11 published cases of immunotactoid
glomerulopathy to date. By immunofluorescence, predominantly
capillary wall, thick, ribbon-like glomerular deposits
contained IgG, IgM, kappa and lambda light chains of equal
intensity, C3, C4 and fibrin related antigens. Mild to
moderate glomerular cell proliferation associated with
nodular sclerosis has been assumed to be causally related to
immunotactoid deposits.
•King JA, Culpepper RM, Corey GR, Tucker JA,
Lajoie G, Howell DN: Glomerulopathies with fibrillary
deposits. Ultrastruct Pathol 2000 Jan-Feb;24(1):15-21.
Department of Pathology, University of South Alabama, Mobile
36617-2293, USA. jking@usamail.usouthal.edu
Renal diseases involving glomerular deposits of fibrillary
material are an important diagnostic challenge for the
ultrastructural pathologist. Two primary disorders of this
type, termed "fibrillary glomerulonephritis" (characterized
by fibrils measuring approximately 20 nm in diameter) and
"immunotactoid glomerulopathy" (characterized by larger,
microtubular deposits), have been described. The possible
relatedness of these two disorders and their potential
association with other systemic illnesses are subjects of
current debate. Other multisystemic diseases, including
amyloidosis and various forms of cryoglobulinemia, can also
present with fibrillary or microtubular deposits in the
kidney. Five cases are presented in which fibrillar or
microtubular structures were identified in renal biopsies by
ultrastructural examination. The distinction between
fibrillary glomerulonephritis, immunotactoid glomerulopathy,
and other processes that have similar ultrastructural
features are discussed.
•Korbet SM, Schwartz MM, Rosenberg BF, Sibley RK,
Lewis EJ. Immunotactoid glomerulopathy. Medicine (Baltimore)
1985 Jul;64(4):228-43. We present 11 patients with
immunotactoid glomerulopathy, a new syndrome characterized
clinically by proteinuria (11/11), microscopic hematuria
(9/11) and hypertension (9/11). The patients consisted of
six females and five males, aged 25 to 59 years (mean,
44.6). Proteinuria was the presenting feature and the reason
for renal biopsy in all patients. The diagnosis of
immunotactoid glomerulopathy was established at renal biopsy
by the presence of glomerular extracellular microtubules
composed of immune reactants. All the biopsies studied by
immunofluorescence (10 cases) had glomerular deposits of IgG
and C3. In three biopsies studied with IgG subclass specific
antisera, only one patient had monoclonal immunoglobulin
deposits (IgG3 kappa). In six cases the glomerular deposits
were analyzed for light chains. In three the deposits
contained kappa only, and three consisted of both kappa and
lambda. In two cases the immune aggregates were confined to
the mesangium, and in the remaining eight cases, the
deposits were present in the mesangium and the glomerular
basement membranes. Electron-dense deposits composed of
microtubules were present in the same distribution within
the glomerulus as the immune reactants. The microtubules had
a uniform diameter in each biopsy, but they varied in size
from case to case. They were approximately the same size in
eight cases (mean, 22.3 +/- 3 [SD] nm). Three cases
had much larger microtubules: 34.2 nm, 35.4 nm, and 48.9 nm
in diameter. Although the 22.3-nm microtubules resembled
amyloid in their appearance, glomerular distribution and
random orientation in the tissue, they were more than twice
the diameter of amyloid (8.9 nm), and Congo red and
thioflavin T stains for amyloid were negative. Similar
microtubular structures have been described in patients with
cryoglobulinemia, SLE and paraproteinemia, but these
diseases were excluded in our patients on clinical,
serologic and in some cases histologic grounds. More
important, none of our patients had clinical or
histochemical evidence of amyloidosis, an entity which may
be confused with immunotactoid glomerulopathy on a
morphologic basis. Follow-up, from 22 to 94 months (mean,
52.6) was obtained in all 11 patients, and 2 clinical
courses were noted. Six patients had progressive
deterioration of renal function, with five requiring
dialysis. This group had severe hypertension (4/6) and
nephrotic-range proteinuria (5/6) at some point in their
course. The remaining five patients with stable renal
function had proteinuria of less than 2.0 g/24 hr in most
cases (4/5), and none had severe hypertension. This
dichotomy correlated with the distribution of
immunotactoids.(ABSTRACT TRUNCATED AT 400 WORDS).
•Markowitz GS, Cheng JT, Colvin RB, Trebbin WM,
D'Agati VD. Hepatitis C viral infection is associated with
fibrillary glomerulonephritis and immunotactoid
glomerulopathy. J Am Soc Nephrol 1998 Dec;9(12):2244-52.
Department of Pathology, Columbia University, College of
Physicians and Surgeons, New York, New York, USA.
The most common form of glomerular disease seen in
association with hepatitis C virus (HCV) infection is
membranoproliferative glomerulonephritis, with or without
associated cryoglobulinemia. This study examines four cases
of fibrillary glomerulonephritis and two cases of
immunotactoid glomerulopathy in association with HCV
infection. Findings at presentation included proteinuria,
renal insufficiency, and hematuria. Renal biopsy revealed a
membranoproliferative pattern of glomerular disease in five
cases, and a membranous glomerulopathy with mesangial
proliferative features in one. On immunofluorescence, all
cases stained with IgG and C3. Electron microscopy revealed
fibrils of the expected diameter, 16 to 28 nm in fibrillary
glomerulonephritis and 33 to 45 nm in immunotactoid
glomerulopathy. In only one case were cryoglobulins detected
(at low titer and on only one of three assays). Antiviral
therapy was not given in any of the six cases. Outcomes were
mixed, with progression to renal failure occurring in two
patients and persistent proteinuria with stable or improved
renal function in three. Follow-up is not available on the
sixth case. Both fibrillary glomerulonephritis and
immunotactoid glomerulopathy have features that overlap with
cryoglobulinemic glomerulonephritis. The relatedness of
these three entities in a subset of patients with HCV
infection suggests a common pathogenic mechanism of
glomerular deposition of organized deposits.
•Monga G, Mazzucco G, Motta M, Quaranta S:
Immunotactoid glomerulopathy (ITGP): a not fully defined
clinicopathologic entity. Ren Fail 1993;15(3):401-5 .
Dipartimento di Scienze Biomediche e Oncologia Umana,
Universita di Torino, Italy.
Immunotactoid glomerulopathy is characterized by the
ultrastructural finding of fibrillary or microtubular
deposits in patients without systemic diseases such as SLE,
diabetes, paraproteinemias, cryoglobulinemia, or
amyloidosis. These deposits correspond in most (but not all)
cases to immunoglobulin and complement deposits as shown by
immunohistochemical techniques. Different light microscopic
patterns (mesangioproliferative, membranous,
membranoproliferative, and crescentic) have been reported.
Clinical presenting feature is characterized by proteinuria
(often of nephrotic range), hematuria, and hypertension in
most cases. Chronic renal failure requiring hemodialysis or
transplantation is described in more than half the patients.
Pathogenesis has not yet been elucidated and only some
speculative hypotheses have so far been suggested. At
present there is no clear evidence that we are dealing with
a new pathologic entity, but larger series must be collected
and studied in order to find a correct taxonomic collocation
of this glomerulopathy.
•Mukai K, Kitazawa K, Totsuka D, Saito K,
Sugisaki T: A case of immunotactoid glomerulopathy with
unusual microtubular deposits. Clin Nephrol 1998
May;49(5):321-4. Department of Nephrology, Showa University
School of Medicine, Tokyo, Japan.
A 57-year-old man with monoclonal gamma-globulinemia was
admitted because of edema and proteinuria. A renal biopsy
specimen showed lobular glomerulonephritis associated with
deposition of material that was positive for IgG, C3, C1q,
fibrin, kappa light chain, and lambda light chain but was
not stained by Congo red. Glomeruli showed massive
electron-dense deposits with two kinds of unusual, highly
organized crystalline structures in the mesangial matrix and
peripheral capillary loops. Clinically, the patient had
nephrotic syndrome, microscopic hematuria, and hypertension.
No Bence-Jones protein or cryoglobulin was found in the
urine or serum. Immunoelectrophoresis of blood and urine
revealed increased IgG-lambda paraprotein, but no free light
chains were found. This case was not associated with
amyloidosis, systemic lupus erythematosus, light chain
deposition disease, cryoglobulinemia, or multiple myeloma.
Immunotactoid glomerulopathy was diagnosed. Treatment with
oral prednisone was effective for the management of
nephrotic syndrome and renal dysfunction. Glomerular
deposition of two kinds of microtubular structure in
immunotactoid glomerulopathy has rarely been
reported.
*Orfila C, Meeus F, Bernadet P, Lepert JC, Suc JM:
Immunotactoid glomerulopathy and cutaneous vasculitis. Am J
Nephrol 1991;11(1):67-72. Toulouse-Rangueil, France.
A 22-year-old woman presented glomerulonephritis with
Schonlein-Henoch-like syndrome and monoclonal abnormality.
One month later, she developed a rapidly progressive
glomerulonephritis with hypertension and persistent purpura.
In the two renal biopsies performed during the first and the
second attack, mesangial expansion and thickening of the
glomerular capillary walls (associated with 50% of crescents
in the second biopsy) were observed on light microscopy. By
immunofluorescence faint deposits of immunoglobulins (light
and heavy chains) and complement components were found
present in the mesangium. Electron microscopy showed tubular
microfibrils measuring 19-24 nm in the mesangium,
subendothelial and subepithelial areas. A skin biopsy
performed during the first attack demonstrated
leukocytoclastic skin vasculitis. By immunofluorescence, no
deposits were observed. Congo red staining for amyloid and
cryoglobulinemia were negative. This case is similar to an
entity recently described and named immunotactoid
glomerulopathy.
•Strom EH, Hurwitz N, Mayr AC, Krause PH,
Mihatsch MJ: Immunotactoid-like glomerulopathy with massive
fibrillary deposits in liver and bone marrow in monoclonal
gammopathy. Am J Nephrol 1996;16(6):523-8. Institute
for Pathology, University of Basel, Switzerland.
At autopsy, massive nonamyloid fibrillar deposits,
immunoreactive to IgG and kappa light chain, were found in
glomeruli, liver, and bone marrow of a 72-year-old woman.
The patient suffered from severe nephrotic syndrome,
hepatomegaly and cholestasis, normochromic anemia, and IgG
kappa monoclonal gammopathy. Fibrillary glomerulopathies,
most often denoted as fibrillary glomerulonephritis or
immunotactoid glomerulopathy, are generally considered to
have deposits restricted to the glomeruli. However, this
study indicates that fibrillary deposits may be a systemic
manifestation of fibrillary glomerulonephritis or
immunotactoid glomerulopathy, at least when the patient is
suffering from a monoclonal gammopathy.
•van Ginneken EE, Assmann KJ, Koolen MI,
Jansen JL, Wetzels JF. Fibrillary-immunotactoid
glomerulopathy with renal deposits of IgAlambda: a rare
cause of glomerulonephritis. Clin Nephrol 1999
Dec;52(6):383-9. Department of Internal Medicine, Bosch
Medicentrum, 's-Hertogenbosch, University Hospital Nijmegen,
Netherlands.
We describe a 24-year-old patient who presented with a
nephrotic syndrome. His renal biopsy revealed a diffuse
mesangioproliferative glomerulonephritis with eosinophilic
deposits. Electron microscopy showed organized, Congo-red
negative deposits, forming microtubules of about 20 nm width
in the capillary walls and in the mesangium, establishing a
diagnosis of fibrillary-immunotactoid glomerulopathy.
Fibrillary-immunotactoid glomerulopathy is a rare cause of
glomerulonephritis, characterized by Congo-red-negative
glomerular deposits of fibrils, sometimes organized in
microtubules, predominantly containing IgG and C3. Patients
clinically present with the nephrotic syndrome, hematuria
and hypertension. The pathogenesis of this glomerulopathy
has not been elucidated yet. In our patient, the renal
deposits contained IgAlambda. This peculiar feature is
suggestive of an underlying paraproteinemia. However, in the
serum no paraproteins or cryoglobulins were found, and also
microscopical examination and immunophenotyping of the bone
marrow did not point to the presence of a monoclonal plasma
cell dyscrasia. Our patient was not treated with
immunosuppressive drugs and he is currently progressing to
end-stage renal disease.
Jones D, Bhatia VK, Krausz T, Pinkus GS:
Crystal-storing histiocytosis: A disorder occurring in
plasmacytic tumors expressing immunoglobulin kappa light
chains. Hum Pathol 30: 1441-1448, 1999
Yamamoto T, Hishida A, Honda N, Ito I, Shirasawa H,
Nagase M: Crystal-storing histiocytosis and crystalline
tissue deposition in multiple myeloma. Arch Pathol Lab Med
115: 351-354, 1991
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