Clinical characteristics, radiological features and outcomes in pulmonary involvement of cryoglobulinemia.

BACKGROUND: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood. METHODS: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia. RESULTS: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001). CONCLUSIONS: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.

Hepatitis B virus-related cryoglobulinemia: Clinical characteristics, virological features, and treatment.

BACKGROUND: Hepatitis B virus (HBV) infection is a rare etiology of cryoglobulinemia, and its clinical characteristics, virological features and treatment are poorly understood. METHODS: This retrospective study enrolled 23 patients with HBV-related cryoglobulinemia from 497 cryoglobulinemia patients at Peking Union Medical College Hospital between January 2015 and February 2023. We analyzed the clinical characteristics, virological features and management of patients with HBV-related cryoglobulinemia. RESULTS: The 23 patients (13 males; median age 48 years) were all mixed cryoglobulinemia and serological HBsAg positive, while 15 patients exhibited HBV-DNA replication. The presence of HBsAg in cryoglobulins was evaluated in 7 patients, all of whom were positive. The most commonly involved organs were kidneys (69.6%), skin (65.2%), peripheral nerves (21.7%), joints (8.7%), gastrointestinal tract (4.3%), and cardiac (4.3%). Eight patients received antiviral therapy with nucleot (s)ide analogues (NAs) alone, 12 patients received NA- and corticosteroid-based regimens, and 3 patients received NA- and rituximab-based regimens based on the severity of clinical symptoms. After a median follow-up of 44 months, four patients died, and one patient was lost to follow-up. All remaining patients (n = 18) achieved clinical remission, and HBV-DNA replication was not detected in 16 out of 18 patients. There was no HBV reactivation in patients treated with rituximab. The three-year overall survival and progression-free survival were 87.0% and 80.3%, respectively. CONCLUSIONS: HBV-related cryoglobulinemia patients should be treated with antiviral therapy. Corticosteroids and rituximab are effective for severe cases, but patients need to be closely monitored for therapy-related infection.

A 47-Year-Old Woman With Progressive Exertional Dyspnea and Fatigue.

CASE PRESENTATION: A previously healthy 47-year-old nonsmoking woman was admitted to our hospital with an 8-month history of progressive exertional dyspnea and fatigue. Chest high-resolution CT (HRCT) on admission showed diffuse, bilateral, patchy ground-glass opacity (GGO) (Fig 1A). She was diagnosed with interstitial lung disease, and corticosteroid therapy with 8 weeks prednisone taper was completed, with initial good response. Eight months later, she was readmitted because of worsening of the dyspnea, with no fever, wheeze, dry cough, chest pain, weight loss, or hemoptysis. She denied a history of hair loss, skin rash, oral ulcers, or arthralgia. She denied a history of allergy or taking other drugs. She had no occupational or environmental exposures. There was no family history of respiratory diseases or hematologic diseases.

Clinical characteristics and treatment outcome of type I cryoglobulinemia in Chinese patients: a single-center study of 45 patients.

To explore the clinical characteristics and outcomes in Chinese patients with type I cryoglobulinemia (CG), we retrospectively analyzed the clinical data, management, and outcomes of 45 patients diagnosed with type I CG in our hospital from January 2015 to March 2019. In our study, all type I CGs were secondary to hematologic diseases, and monoclonal gammopathy of unknown significance was the most common primary disease, accounting for 48.9% (n = 22). Additionally, B cell non-Hodgkin lymphoma, Waldenström's macroglobulinemia, and multiple myeloma accounted for 24.4% (n = 11), 20.0% (n = 9), and 6.7% (n = 3), respectively. In patients with type I CG, skin damage was the most common symptom, presenting in 57.8% of the patients, followed by peripheral neuropathy (22.2%) and renal involvement (15.6%). Treatment was initiated in 29 patients (64.4%), and the most common choice was a rituximab-based regimen in 13 patients (44.8%), followed by bortezomib-based regimen in 11 patients (37.9%). Clinical symptoms were significantly improved after treatment, and the clinical remission rate was 86.2%, including 34.5% of complete clinical remission, while the laboratory response rate was 88.9%, including 33.3% of complete response and 55.6% of partial response. The expected 1-year overall survival was 97.8%. In conclusion, for patients with multisystemic involvement, such as skin damage, kidney damage, or peripheral neuropathy, the diagnosis of type I CG should be considered, and the underlying disease needs to be explored. Symptoms and primary diseases should be taken into consideration before choosing initial management.

[Preliminary study on pro-apoptotic gene BAD of Schistosoma japonicum].

OBJECTIVE: To understand the characteristics of pro-apoptotic gene SjBAD of Schistosoma japonicum, such as its biology, immunology, and transcriptional expression, and evaluate its potential of the recombinant protein as a vaccine candidate for schistosomiasis. METHODS: SjBAD was amplified by PCR and subeloned into a pET-28a(+) vector, and the recombinant plasmid was transformed into competent E. coli BL21 for producing recombinant protein. The expressions of SjBAD in different development stages of schistosomula and 42-day male and female worms were determined by real-time PCR. The immunogenicity of the recombinant protein was analyzed by Western blotting and ELISA. The potential of this protein as a vaccine candidate molecule was assessed by testing the worm reduction rate and liver egg reduction rate in the BALB/c mice immunized by the recombinant antigen SjBAD. RESULTS: SjBAD was successfully cloned, the recombinant plasmid pET-28a(+)-SjBAD was successfully expressed in E. coli, and the molecular weight of the recombinant protein was around 22 kDa. Western-blotting showed that the recombinant protein had good immunogenicity. The recombinant protein could induce high level of specific IgG antibodies in the BALB/c mice. SjBAD was expressed in all tested 7-, 14-, 21-, 28-, 35- and 42-day worms, and was highly expressed in 14-day schistosomula, while the expression level in 42-day male worms was higher than that in 42-day female worms. Two in- dependent animal trials showed that 30.82% and 27.87% worm reduction rates, as well as 42.52% and 45.84% liver eggs reduction rates were obtained in the rSjBAD vaccinated group compared with those of the blank control group (both P < 0.05). CONCLUSIONS: The proapoptotic gene SjBAD is successfully cloned and expressed. The gene is expressed in different development stages of S. japonicum. The rSjBAD vaccinated BALB/c mice can obtain a partial protective immunity against S. japonicum infection.

[Cloning, expression and immuno-protection analysis of a gene encoding troponin T of Schistosoma japonicum (SjTnT)].

OBJECTIVE: To clone cDNA encoding troponin T of Schistosoma japonicum (SjTnT), and evaluate the protective efficacy induced by recombinant SjTnT in BALB/c mice against S. japonicum challenge infection. METHODS: The SjTnT gene was amplified from 28-day-schistosome cDNAs by PCR and then subcloned into pET28a(+). The recombinant SjTnT protein (rSjTnT) was expressed in Escherichia coli BL21 (DE3) cells. The serum specific to rSjTnT was prepared by immunized BALB/c mice with the recombinant antigen, and the immunogenicity of rSjTnT was detected by Western blotting and ELISA. The immuno-protective efficacy induced by rSjTnT in BALB/c mice was evaluated according to the reduction in worm and egg counts. RESULTS: The cDNA encoding SjTnT was successfully cloned and expressed in E. coli. Western blotting showed that rSjTnT had a good immunogenicity. The high level of specific IgG antibodies was detected, and 33.89% worm reduction and 43.94% liver egg reduction were obtained in mice vaccinated with rSjTnT combined with Seppic 206 adjuvant compared with those in the adjuvant control group. CONCLUSIONS: rSjTnT could induce partial immuno-protection against S. japonicum infection in BALB/c mice. This study provided a basic for understanding the biological function of SjTnT.