Transcript Heavy chain deposition disease in kidney biopsies (PPT / 13064.5 KB)

Heavy chain deposition
disease in kidney biopsies
Alenka Vizjak, Jerica Mraz, Jelka Lindič,
Dušan Ferluga
Institute of Pathology, Faculty of Medicine
University of Ljubljana, Slovenia
Disclosures: no conflicts of interest
Heavy chain deposition disease
(HCDD)
• HCDD - a rare monoclonal immunoglobulinrelated disorder of not yet fully explored
pathogenesis
• Characterized by production and systemic
deposition of structurally abnormal
immunoglobulin heavy chains, while light
chains absent in the deposits
• First described by Aucouturier et al
(N Engl J Med 1993; 329: 1389-93)
Monoclonal immunoglobulin
deposits in the kidney
Amyloid
deposits
Non-amyloid monoclonal
immunoglobulin deposits
Amyloidosis MIDD Randall-type GN with monoclonal
LC
LCDD
Igs dps mimicking
IC-GN
HC (very
LHCDD
rare)
Cryoglobulinemic-GN
HCDD
Immunotactoid GP /
fibrillary GN
Patients and methods
• 4 biopsy cases of HCDD (5 kidney biopsies;
1 autopsy), representing 0.09% prevalence
among 5481 native kidney biopsies
• All 4 female patients, age range 62 – 79 yrs,
mean age 73.0 yrs
• Standard light microscopy
• Immunofluorescence microscopy
IgA, IgG, IgM, κ, λ, C3, C1q, fibrin/fibrinogen,
albumin
IgG1, IgG2, IgG3, IgG4, γCH1, γCH2, γCH3
• Electron microscopy
Clinical presentation / diagnosis in
4 patients with HCDD
Pts
At kidney biopsy
After kidney biopsy
PM - 1st CKD, prot, compl↓
no dysproteinemia
PM - 2nd CKD, NS, compl↓
no dysproteinemia
JA
CKD, prot, compl↓
plasmocytoma
BŠ
RPGN, NS, compl↓
plasmocytoma
RM
CKD, nephr prot,
compl norm
no dysproteinemia
CKD – chronic kidney disease, NS – nephrotic syndrome
Immunofluorescence microscopy in
4 cases of HCDD
γCH1 γCH2
subclass
γCH3
κ/λ
C3
C1q
n.d.
2+ / ±
2+
4+
0
4+
0/0
2+
4+
IgG3
0
3+
0/0
4+
3+
4+
IgG3
0
4+
0/0
3+
4+
4+
IgG1
0
4+
0/0
4+
3+
Pts
IgG
(γ)
IgG
PM - 1st
4+
n.d.
n.d.
PM - 2nd
4+
IgG3
JA
3+
BŠ
RM
Light and electron microscopy in
4 cases with HCDD
Light microscopy
•Diffuse nodular glomerulosclerosis
•Glomerular capillary aneurysms
•Mesangial proliferation,
with segm endo-, membranoprol pattern
•Extracapillary crescents (few)
4/4
4/4
4/4
3/4
2/4
Electron microscopy
•Punctate and powdery
electron dense deposits
3/4
IgG (γ heavy chain)
κ, λ light chains
IgG (γ heavy chain)
IgG1
IgG2
C3
C1q
γCH1
γCH2
SMA+CD31
CD68
Conclusions of our study
• Immunofluorescence examination of kidney
biopsy, including testing for Igs heavy and light
chains, as well as IgG subclasses, is crucial for
the diagnosis of HCDD.
• Our study showed that HCDD is peculiar among
MIDD because of uniform pattern of nodular
glomerulosclerosis with pronounced capillary
aneurysms and significant proliferation due to
complement activation.
• Constant deletion of the gamma heavy chain
CH1 domain and its significance in the
pathogenesis of HCDD was confirmed.