Immunoglobulin subtyping and quantification in direct antiglobulin test: positive haemolysis in an HIV-prevalent setting

AimsPositive direct antiglobulin tests (DATs) are valuable in identifying the aetiology of autoimmune haemolysis and in guiding therapeutic intervention. However, in HIV-positive individuals with background polyclonal gammopathy, a positive DAT in the absence of haemolysis is common. In this setting, IgG quantification and subtyping may be of value, as this is possible with the recently introduced gel cards. There is paucity of literature evaluating the diagnostic usefulness of IgG subtyping and quantification in HIV-positive individuals who are investigated for autoimmune haemolytic anaemia (AIHA). This study evaluated the usefulness of IgG quantification and subtyping in the diagnostic work-up of AIHA in patients with a positive DAT, with and without HIV infection.MethodsThis retrospective, cross-sectional study included patients investigated for AIHA in a quaternary care hospital. Those with a positive DAT had their IgG subtyped and quantified using the ID-Card DAT IgG1/IgG3 and IgG-dilution cards (Bio-Rad, Cressier, Switzerland).ResultsNinety patients admitted from December 2019 to March 2020 were investigated for AIHA. Forty-four (49%) patients had a positive DAT of whom 26 (59%) had evidence of haemolysis, and 16 (36%) were HIV positive. Concurrent HIV and haemolysis were present in eight patients, two of whom had IgG1 although none had an IgG antibody titre >1:30. None of the HIV-positive patients without features of haemolysis had IgG1/IgG3 or IgG antibody titres >1:30.ConclusionIn our clinical setting, IgG quantification and subtyping were found to be of limited value in the diagnostic characterisation of AIHA in HIV-positive patients with false-positive DAT.

Immunoglobulin Abnormalities in Gaucher Disease: an Analysis of 278 Patients Included in the French Gaucher Disease Registry

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40–9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

Serum protein electrophoresis pattern in patients living with HIV: frequency of possible abnormalities in Iranian patients

Background and Objectives: This prospective case-control study was conducted to evaluate abnormal serum protein electrophoresis (SPEP) patterns in patients living with human immunodeficiency virus (HIV) and its relation with disease severity markers and anti-retroviral treatment status. Materials and Methods: Thirty-seven HIV-positive patients and 24 healthy individuals were evaluated in the course of this study. The healthy HIV-negative individuals were selected as control group. Pregnant women, patients with malignancies, children, hepatitis B- and/or C-positive patients, those with a history of an autoimmune disease, or previous corticosteroid administration were excluded. SPEP—which detects serum levels of albumin, total protein, gammaglobulin—, CD4+ T-cell counts, viral load, and antiretroviral treatment status were assessed. Data were analyzed by SPSS™ software. Results: Twelve patients (32 percent) demonstrated polyclonal gammopathy on SPEP, while only 1 (4 percent) healthy individual had the same pattern (P-value = 0.007). No statistically significant connection between SPEP patterns and antiretroviral treatment status was observed (P-value > 0.05). Interestingly no statistically significant relationship between CD4+ T-cell counts and polyclonal gammopathy was discerned. No statistically significant difference was observed between the two groups with regards to serum albumin and total protein levels. The serum albumin to total protein percentage, serum gamma globulin to total protein percentage, and serum albumin to globulin ratio was compared between the groups and a statistically significant difference was observed. Conclusion: Polyclonal gammopathy on SPEP is common among HIV-infected patients. Moreover, the SPEP patterns cannot be used as an indication of a patient’s negative or positive response to treatment.

Thoracic and paraspinal extramedullary hematopoiesis in a cat with chronic non-regenerative anemia

Case summary A 6-year-old neutered male domestic shorthair cat presented with non-regenerative macrocytic anemia of 2 years’ duration and minimally ambulatory paraparesis. Neurologic examination suggested an upper motor neuron paresis or T3–L3 myelopathy. The cat was positive for feline immunodeficiency virus (FIV), neutropenic, had polyclonal gammopathy and was euthanized following a hemolytic crisis. At autopsy, multifocal bilateral dark red masses were observed subpleurally around the costochondral junctions, extradurally and paraspinally in the spinal canal, and paravertebrally, on the lateral and ventral subpleural surfaces of the T4–11 vertebrae. Histologic examination of the masses revealed extramedullary hematopoietic tissue composed primarily of erythroid precursors and megakaryocytes, with occasional myeloid precursors and blood-filled sinuses. Bone marrow findings supported ineffective granulopoiesis, and decreased erythropoiesis and megakaryopoiesis, with probable myelodysplasia as the underlying cause of the hematologic abnormalities. Relevance and novel information Thoracic, paraspinal and paravertebral extramedullary hematopoietis presenting as masses has not been described previously in cats with chronic anemia. This is a unique case of a thoracic–spinal–epidural extramedullary hematopoietic masses resulting in possible spinal cord compression and paraparesis in a cat.

Case Report of a 21-Year-Old Man With Epidermolysis Bullosa Acquisita

Epidermolysis bullosa acquisita (EBA) is a rare acquired type of mechanobullous disease affecting the dermal-epidermal junction (DEJ) of trauma prone acral surfaces. It manifests as tense vesicles, bullae, and milia and typically heals as atrophic hypo- or hyperpigmented scars. Classic noninflammatory mechanobullous EBA typically presents at a mean age of 48 years. A 21-year-old man presented with a 2-year history of nonpainful papular-vesicular lesions on his hands, knees, and toes after minor trauma to these areas. Physical exam revealed postinflammatory hypopigmented scarring and milia to the bilateral dorsal hands and bilateral extensor elbows and knees, with tense blisters on the dorsal hand and patella regions. Direct immunofluorescence revealed strong linear IgG and IgM with weak focal positivity for IgA and C3 at the DEJ. Blood work revealed an increased diffuse gamma region of 71 g/L (6-13 g/L) on serum protein electrophoresis. Pathology showed a fibrotic underlying dermis, with subepidermal bullae and separation and no significant inflammation. The patient was started on colchicine. This case showcases an unusual early age of presentation for mechanobullous EBA and illustrates the importance of interpreting pathology in the context of clinical findings and maintaining a high index of suspicion for EBA in younger patients who present with classic findings. This case is unique as it is the first report of an association between EBA and polyclonal gammopathy and could be suggestive of chronic inflammation, which would fit with our patient’s chronic history of EBA.