Immunotactoids and fibrillary glomerulopathy N08.1

Group of very rare glomerular diseases consisting of immunotactic glomerulopathy (ITG) and non-amyloid fibrillary glomerulopathy (FGP) characterized by mesangial accumulations of monoclonal microtubular or polyclonal fibrillary deposits. The diagnosis is a diagnosis of exclusion.

ITG and FGP are found in 0.6% of all renal biopsies; non-amyloid fibrillary glomerulopathy (FGP) is 10 times more common than immunotactic glomerulopathy (ITG); m:w= 1:1.

The pathomechanism is unknown. ITG is more often associated with an underlying lymphoproliferative disease, hypocomplementary, dysproteinemia, monoclonal gammopathy or occult cryoglobulinemia than FGP. Associations with progressive systemic scleroderma as well as Sjögren's syndrome have been described (Sehgal R et al. 2017). The deposition of immunoglobulins (especially of IgG kappa and lambda light chains as well as C3) also suggest a functional disorder of the immune system.

Average age at first diagnosis is about 45 years. The disease has also been described in children and adolescents.

Slightly more than 50% of patients are clinically conspicuous by renal insufficiency at the time of initial diagnosis. Proteinuria is always detectable. This is > 60% in the nephrotic area. Further evidence of microhaematuria (60%) and hypertension (70%).

Findings of both nephritic and nephrotic syndrome. C3 and C4 in the serum may be decreased.

Signs of membranous glomerulonephritis or membranoproliferative glomerulonephritis detectable. Mesangial expansion due to amorphous eosinophilic depositions and low mesangial cell accumulation. No amyloid detection (Congo red staining for amyloid is negative).

IgG and C3, more rarely kappa and lambda light chains can be detected immunohistologically.

Recently, with the immune marker "DNAJB9" a sensitive and specific marker for FGP seems to be available (Nasr SH et al. 2017).

EM: Detection of non-amyloid, microfibrillary or microtubular structures in the renal mesangium and at the glomerular basement membrane. In fibrillar glomerulopathy, the diameter of the microfibrils and microtubules varies between 20 and 30 nm. In immunotactoid glomerulopathy, the diameter of the microfibrils and microtubules varies between 30 and 50 nm.

Clinic, lab, kidney biopsy.

Targeted treatment of a haematological (or autoimmunological) systemic disease. ACE inhibitors or angiotensin II receptor blockers, immunosuppressants and/or corticosteroids may be used. The success is doubtful. Immunosuppressants have been used - based on individual case reports - but are not a mainstay of therapy. Retuximab was successful in individual cases (Karasawa K et al. 2018).

The disease usually progresses slowly to renal insufficiency and leads to terminal kidney disease in 50% of patients within 1-10 years (Sehgal R et al. 2017). In the presence of hypertension, proteinuria in the nephrotic area and renal insufficiency at initial diagnosis, a faster progression must be expected.

It is assumed that there are only gradual differences between fibrillary (FGP) and immunotactoid (ITG) glomerulopathy.

Due to the electron microscopic findings with the presence of microtubular (in contrast to smaller microfibrillary in FGP) structures in the deposits, some authors distinguish immunotactoid from fibrillary glomerulopathy.

1. Hirashio S et al, (2018) A case of immunotactoid glomerulopathy with false-negative IgG staining. BMC Nephrol 19:143.
2. Karasawa K et al (2018) Successful treatment with rituximab of immunotactoid glomerulopathy exhibiting nephrotic syndrome
. Clin Nephrol 90:222-226.
   Motwani SS et al. (2016) Paraprotein-Related Kidney Disease: Glomerular Diseases Associated with Paraproteinemias. Clin J Am Soc Nephrol 11:2260-2272.
3. Nasr SH et al (2017) DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. Kidney Int Rep 3:56-64.
4. Sehgal R et al (2017) Fibrillary Glomerulonephritis in Primary Sjogren's Syndrome: A Rare Cause of Renal Failure. Clin Med Res 15(3-4):100-105.