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A considerable number of patients with high clinical suspicion for cryoglobulinaemic vasculitis either show negative results for the detection of cryoglobulins or show only trace amounts which cannot be characterized for composition. We aimed at establishing whether the failure to detect or the detection of trace amounts of cryoglobulin with conventional methods either identifies a peculiar subset of low level cryoglobulinaemia (from now on hypocryoglobulinaemia) or represents a separate entity. Using a modified precipitation technique in hypo-ionic medium, we prospectively identified between 2008 and 2021 237 patients (median age 60.8 years [22–97], 137 females) having < 0.5% cryocrit and clinical suspicion of autoimmune disorder. Of these 237 patients, only 54 (22.7%) had a history of HCV infection. One hundred and sixty-nine out of 237 patients (71%) had an established underlying disease, while 68 patients (28.6%) (median age 62.9 years [29–93], 35 females) did not show either laboratory markers or clinical symptoms consonant with an underlying aetiology. These 68 cases with only trace amounts of cryoglobulins were defined as having a putatively idiopathic hypocryoglobulinaemia. Nineteen of these 68 patients (27.9%) had a history of HCV infection. Twenty-four patients out of 68 (35.3%) were positive for rheumatoid factor (RF), while 25 (36.7%) patients had signs of complement consumption (i.e., C4 < 15 mg/dl and/or C3 < 80 mg/dl), and 36 (52.9%) had increased inflammatory indexes. Seven patients only had arthralgia and constitutional symptoms while 61 out of 68 (89.7%) presented with at least one of the three cardinal signs of cryoglobulinaemic vasculitis including skin lesions, peripheral nerve involvement, and glomerulonephritis. Seventy-five percent of the subjects had type III hypocryoglobulins. In patients with hypocryoglobulinaemia the histologic features of glomerulonephritis (also examined by electron microscopy) resembled those of mixed cryoglobulinaemia-associated glomerulonephritis. In conclusion, hypocryoglobulins are often polyclonal and are mainly unrelated to HCV infection. Patients who present high clinical suspicion for vasculitis, especially glomerulonephritis and yet test negative for cryoglobulinaemia detected by standard techniques, could require deeper investigation even in the absence of HCV infection, RF activity or signs of complement consumption. [ABSTRACT FROM AUTHOR]

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by a challenging diagnostic workup requiring ultrastructural identification of 20 nm-thick randomly oriented fibrillar deposits. However, the recent introduction of DNAJB9 as a putative diagnostic marker of FGN could thoroughly improve this diagnostic scenario. This study aims to assess the DNAJB9 immunohistochemical expression in a large series of FGN cases and to eventually confirm its role as a diagnostic marker of FGN. We evaluated the immunohistochemical expression of DNAJB9 (Rabbit Polyclonal, ThermoFisher) in a series of 77 FGN and 128 non-FGN cases diagnosed between January 1992 and June 2022 at the Pathology Unit of the AOU Città della Salute e della Scienza Hospital. DNAJB9 was expressed in 73 of the 74 evaluable FGN cases, mostly showing a strong glomerular positivity (68 cases). Additionally, DNAJB9 resulted positive in all challenging scenarios [early-stage (6), congophilic (4), combined (4), and uncertain (4) cases of FGN)]. DNAJB9 was negative in all non-FGN cases, eventually resulting in a specificity of 100% and sensitivity of 99%. In conclusion, we confirmed the role of DNAJB9 as a diagnostic marker of FGN. Its adoption in the clinical routine will allow a faster, more feasible, and more accurate FGN diagnosis. [ABSTRACT FROM AUTHOR]

The onset of coronavirus disease (COVID-19) as a pandemic infection, has led to increasing insights on its pathophysiology and clinical features being revealed, such as a noticeable kidney involvement. In this study, we describe the histopathological, immunofluorescence, and ultrastructural features of biopsy-proven kidney injury observed in a series of SARS-CoV-2 positive cases in our institution from April 2020 to November 2021. We retrieved and retrospectively reviewed nine cases (two pediatric and seven adults) that experienced nephrotic syndrome (six cases), acute kidney injury (two cases), and a clinically silent microhematuria and leukocyturia. Kidney biopsies were investigated by means of light microscopy, direct immunofluorescence, and electron microscopy. The primary diagnoses were minimal change disease (four cases), acute tubular necrosis (two cases), collapsing glomerulopathy (two cases), and C3 glomerulopathy (one case). None of the cases showed viral or viral-like particles on ultrastructural analysis. Novel and specific histologic features on kidney biopsy related to SARS-CoV-2 infection have been gradually disclosed and reported, harboring relevant clinical and therapeutic implications. Recognizing and properly diagnosing renal involvement in patients experiencing COVID-19 could be challenging (due to the lack of direct proof of viral infection, e.g., viral particles) and requires a proper integration of clinical and pathological data. [ABSTRACT FROM AUTHOR]