Systemic lupus erythematosus combined with Wilson's disease: a case report and literature review.

BACKGROUND: Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. CASE REPORT: We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. CONCLUSIONS: SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.

Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism.

Nonalcoholic steatohepatitis (NASH) is a condition that progresses from nonalcoholic fatty liver disease (NAFLD) and is characterized by hepatic fat accumulation, inflammation, and fibrosis. It has the potential to develop into cirrhosis and liver cancer, and currently no effective pharmacological treatment is available. In this study, we investigate the therapeutic potential of targeting ceruloplasmin (Cp), a copper-containing protein predominantly secreted by hepatocytes, for treating NASH. Our result show that hepatic Cp is remarkedly upregulated in individuals with NASH and the mouse NASH model. Hepatocyte-specific Cp ablation effectively attenuates the onset of dietary-induced NASH by decreasing lipid accumulation, curbing inflammation, mitigating fibrosis, and ameliorating liver damage. By employing transcriptomics and metabolomics approaches, we have discovered that hepatic deletion of Cp brings about remarkable restoration of bile acid (BA) metabolism during NASH. Hepatic deletion of Cp effectively remodels BA metabolism by upregulating Cyp7a1 and Cyp8b1, which subsequently leads to enhanced BA synthesis and notable alterations in BA profiles. In conclusion, our studies elucidate the crucial involvement of Cp in NASH, highlighting its significance as a promising therapeutic target for the treatment of this disease.

Is aceruloplasminemia treatable? Combining iron chelation and fresh-frozen plasma treatment.

We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

Aceruloplasminemia: a rare disease - diagnosis and treatment of two cases

Aceruloplasminemia is a rare autosomal recessive disease in which a mutation leads to the absence or dysfunction of ceruloplasmin. Deficiency of this enzyme leads to the accumulation of iron in various organs; aceruloplasminemia is usually characterized by diabetes, retinal degeneration and neurological disorders. Diagnosis is suspected by the presence of elevated levels of ferritin, anemia, decreased serum copper and absence of ceruloplasmin in serum. Treatment of aceruloplasminemia is mainly based on the control of iron overload.

Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage.

CNS injury-induced hemorrhage and tissue damage leads to excess iron, which can cause secondary degeneration. The mechanisms that handle this excess iron are not fully understood. We report that spinal cord contusion injury (SCI) in mice induces an "iron homeostatic response" that partially limits iron-catalyzed oxidative damage. We show that ceruloplasmin (Cp), a ferroxidase that oxidizes toxic ferrous iron, is important for this process. SCI in Cp-deficient mice demonstrates that Cp detoxifies and mobilizes iron and reduces secondary tissue degeneration and functional loss. Our results provide new insights into how astrocytes and macrophages handle iron after SCI. Importantly, we show that iron chelator treatment has a delayed effect in improving locomotor recovery between 3 and 6 weeks after SCI. These data reveal important aspects of the molecular control of CNS iron homeostasis after SCI and suggest that iron chelator therapy may improve functional recovery after CNS trauma and hemorrhagic stroke.

[Role of the antioxidant ceruloplasmin in complex intensive therapy for severe posthemorrhagic complications in cancer surgery].

The paper summarizes the results of 10 years' experience in using the biocompatible antioxidant ceruloplasmin in cancer patients to prevent and treat life-threatening complications in critical states caused by various complications after extensive surgical interventions for malignant tumors or massive intraoperative blood loss. Hemorrhagic shock-complicated intraoperative massive blood loss is shown to exert a significant damaging effect on the redox system, which correlates with the objectified severity of a critical condition and with the degree of experienced hypoxia. The use of ceruloplasmin in cancer patients with postoperative complications or massive intraoperative blood loss contributes to the recovery of the potential of the antioxidative defense system, to the correction of oxidative stress, acute multiple organ deficiency, and endotoxemia, and to the reduction of the incidence of pyoseptic complications.

[The role of ceruloplasmin in neoplastic processes].

Ceruloplasmin (CP) is a copper containing oxidase of human plasma alpha 2-globulin fraction. The review summarizes literature data on biological role of CP under normal conditions and during development of malignant tumor. This protein may be involved both into antitumor deference and also into metastasizing process. Although CP has already been employed into intensive therapy of oncologic patients all mechanisms underlying its biological activity remain to be clarified.

A fungal multicopper oxidase restores iron homeostasis in aceruloplasminemia.

Mutations that lead to a loss of the copper-containing plasma enzyme ceruloplasmin disrupt mammalian iron homeostasis. The mechanism by which ceruloplasmin mobilizes iron from cell stores has been controversial. We demonstrate that injection of a soluble copper-containing yeast protein Fet3p can restore iron homeostasis in phlebotomized mice with a deletion of the ceruloplasmin gene. These results show the conservation of function of copper-containing proteins in eukaryotic iron metabolism.

[Antioxidants ceruloplasmin and lactoferrin in the prevention and treatment of postoperative complications in cancer patients]. / Antioksidanty tseruloplazmin i laktoferrin v profilaktke i lechenii posleoperatsionnykh oslozhnenii u onkologicheskikh bol'nykh.

Ceruloplasmin and laprote based on natural protein antioxidants were used in the treatment and prevention of postoperative complications in 174 patients after extensive interventions for cancer. Development of pyoseptic complications during the postoperative period is associated with activation of lipid peroxidation, decreased functional activity of the antioxidant component of detoxication, suppressed T-cellular immunity, and development of polyorgan failure in the presence of endogenous toxemia. Systemic treatment with laprote (50 pts) and ceruloplasmin (33 pts) after surgical cleansing and draining of purulent focus stimulated activation of antioxidant defense, decreased the intensity of oxidative processes, normalized the lymphocytic component of immunity, and promoted resolution of polyorgan, primarily hepatic failure. Local therapy with laprote (60 pts) promoted rapid regression of local pyoinflammatory processes. Intraoperative blood loss complicated by hemorrhagic shock had a deep impact on the oxidative/antioxidant system, which correlated with the severity of hypoxia. Addition of ceruloplasmin, a potent antioxidant, to therapy of these patients (n = 31) optimized the course of recovery by stimulating the resolution of posthypoxic polyorgan failure, recovery of the oxidant/antioxidant balance, and decreasing the incidence of postoperative pyoinflammatory complications.

[Efficacy of ceruloplasmin in the resuscitation oncology clinic]. / Effektivnost' tseruloplazmina v reanimatsionnoi onkologicheskoi klinike.

The use of ceruloplasmin in the intensive therapy of oncological patients has been shown to optimize the course of the rehabilitative period promoting dissipating of polyorgan failure, restoration of oxidant-antioxidant balance, reduction in the incidence of pyo-septic complications. Ceruloplasmin is found out to have an apparent detoxicating and antiinflammatory effect, it activities the bodily antioxidant defence, favors normalization of the condition of the immunity lymphocytic link.

[New possibilities in prevention and correction of postoperative suppurative-septic complications and multiple organ failure in oncological surgery]. / Novye vozmozhnosti profilaktiki i korrektsii posleoperatsionnykh gnoino-septicheskikh oslozhnenii i poliorgannoi nedostatochnosti v onkokhirurgii.

The functional status of the oxidative-antioxidative system was studied in 72 patients after vast cancer operations. Traditional surgical treatment and its combination with intraoperative irradiation were shown to lead to tense antioxidative defense and to suppressed T-cell immunity and to call for antioxidative and immunomodulating therapy. High intraoperative blood loss complicated by hemorrhagic shock injured the oxidative-antioxidative system greatly. The magnitude of this damage correlated with the rate of prehypoxia. Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a recovery period, helped to correct posthypoxic multiorgan insufficiency, to recover oxidative-antioxidative balance, and to decrease the incidence of pyoinflammatory complications. Patients with endogenous intoxication showed activated lipid peroxidation, decreased functional activity of antioxidative defense components and of T-cell immunity in homeostasis. The use of Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects on the patient's body and activated its antioxidative defense.

[The use of ceruloplasmin in combination with adjuvant polychemotherapy in stomach cancer]. / Primenenie tseruloplazmina v sochetanii s ad''iuvantnoi polikhimioterapiei pri rake zheludke.

Ceruloplasmin as a modulator was used for the first time in the clinical practice in 30 patients with gastric cancer in the course of postoperative intraabdominal adjuvant chemotherapy. It was established that ceruloplasmin was well tolerated by the patients and its use during polychemotherapy is accompanied by normalization of the levels of natural ceruloplasmin and iron in the blood serum that are usually reduced in patients with gastric cancer, reduces activation of lipid peroxidation and improves the course of postoperative period. Ceruloplasmin possesses a week immunomodulating action in polychemotherapy which is expressed in the increase of the percentage content of T-lymphocytes. Use of ceruloplasmin tended to improve the functional state of the cardiovascular system.

Clinical results on the use of human ceruloplasmin in aplastic anemia.

Frequent blood transfusions are necessary in aplastic anemia because of decreased hematopoietic function. In order to maintain the hemoglobin level and to decrease the need for blood transfusion, human ceruloplasmin was used for the treatment of 73 patients with aplastic anemia. A marked beneficial effect was obtained in 16 cases. The treatment was moderately effective in 17 cases, slightly effective in eight cases, and ineffective in 32 cases. The usual dose of ceruloplasmin was 15 mg/day, but it was varied according to symptoms. Side effects were minimal when ceruloplasmin was administered by slow intravenous injection.