1. 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

2. Heavy chain deposition disease (HCDD)
HCDD - a rare monoclonal immunoglobulin-related 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: )

3. Monoclonal immunoglobulin deposits in the kidney
Amyloid deposits
Non-amyloid monoclonal immunoglobulin deposits
Amyloidosis LC
HC (very rare)
MIDD Randall-type LCDD
LHCDD
HCDD
GN with monoclonal Igs dps mimicking IC-GN
Cryoglobulinemic-GN
Immunotactoid GP / fibrillary GN

4. 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

5. 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↓ JA
plasmocytoma BŠ
RPGN, NS, compl↓ RM
CKD, nephr prot, compl norm
CKD – chronic kidney disease, NS – nephrotic syndrome

6. Immunofluorescence microscopy in 4 cases of HCDD
Pts
IgG (γ)
IgG subclass
γCH1
γCH2 γCH3
κ / λ C3
C1q
PM - 1st 4+
n.d.
2+ / ± 2+
PM - 2nd
IgG3
0 / 0 JA 3+ BŠ RM
IgG1

7. Light and electron microscopy in 4 cases with HCDD
Light microscopy
Diffuse nodular glomerulosclerosis 4/4
Glomerular capillary aneurysms 4/4
Mesangial proliferation, 4/4 with segm endo-, membranoprol pattern 3/4
Extracapillary crescents (few) 2/4
Electron microscopy
Punctate and powdery electron dense deposits 3/4

8. IgG (γ heavy chain) κ, λ light chains

9. IgG (γ heavy chain)

10. IgG IgG2

11. C C1q

12. γCH γCH2

15. SMA+CD CD68

18. 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.