OBJECTIVE: To analyze the change of serum C1q in the course of multiple myeloma (MM) and its correlation with clinical characteristics. METHODS: A total of 138 newly diagnosed MM patients in Zhongnan Hospital of Wuhan University from June 2016 to December 2019 were selected as research objects, during the same period 50 age-matched anemia patients, 50 lymphoma patients, 50 leukemia patients, and 50 myelodysplastic syndrome (MDS) patients were selected as control groups. All the patients met WHO disease classification, and were definitely diagnosed by pathology or bone marrow smear/biopsy. The changes of C1q between MM patients and control group, as well as in different therapeutic responses of MM patients before and after treatment were compared, also the difference of clinical characteristics among MM patients with different C1q level, so as to analyze risk factors which led to C1q decline. RESULTS: The average value of C1q in MM patients was (128.18±51.24) mg/L, which was significantly lower than control group (P<0.01). The levels of white blood cell, platelet (PLT), hemoglobin (Hb), serum calcium, albumin, lactate dehydrogenase (LDH) in newly diagnosed high C1q group were significantly higher than those in low C1q group (P<0.05). Logistic analysis showed that the levels of PLT, Hb, albumin, and LDH in newly diagnosed high C1q group were higher than those in low C1q group (r=0.248, r=0.394, r=0.405, r=0.295). After treatment, the levels of C1q in MM patients with complete remission and very good partial remission were significantly higher than before treatment (P<0.05), while those with partial remission and stable disease also increased but not significantly (P>0.05). CONCLUSION The C1q level in MM patients is significantly lower than that in patients with other hematologic system diseases, and it increases with the remission of the disease after treatment.
Albumins ; Bone Marrow ; Complement C1q ; Humans ; Multiple Myeloma ; Risk Factors

C1q nephropathy is a rare type of glomerulonephritis manifested as the deposition of C1q in the glomerular mesangium during immunofluorescent staining. Systemic lupus erythematosus and type I membranoproliferative glomerulonephropathy need to be excluded in the diagnosis of C1q nephropathy. C1q nephropathy has various manifestations under a light microscope, mainly including minimal change disease, focal segmental glomerulosclerosis, and proliferative glomerulonephritis. This disease is mainly manifested as persistent proteinuria or nephrotic syndrome and occurs more frequently in boys. Currently, glucocorticoids are mainly used for the treatment of this disease. Patients with C1q nephropathy show a good response to immunosuppressant treatment, but have a high rate of glucocorticoid resistance. Therefore, in this case, methylprednisolone pulse therapy or a combination with immunosuppressant treatment helps to achieve a good prognosis.
Complement C1q ; metabolism ; Diagnosis, Differential ; Glomerulonephritis ; diagnosis ; drug therapy ; etiology ; Glucocorticoids ; therapeutic use ; Humans ; Prognosis

The C1q family is one of the subcomponents of the C1 complex that recognizes immune complexes and initiates the classical pathway of the complement system. In addition, as a pattern recognition receptor (PRR), the C1q family binds to a wide variety of ligands. As a member of the C1q family, the secretory C1q includes several subtypes. The main subtypes are cerebellin (Cbln) and C1q-like protein (C1ql). In the nervous system, secretory C1q is involved in the formation and regulation of various types of synapses, thus secretory C1q is closely related to diseases of the central nervous system. In this article, we review the role of secretory C1q in synapse formation and regulation, and its relationship with some diseases of the central nervous system.
Antigen-Antibody Complex ; Central Nervous System ; Complement C1q ; physiology ; Humans ; Synapses ; physiology

Inflammation underlies a wide variety of physiological and pathological processes, and plays a pivotal role in controlling pathogen infection. C1q/tumor necrosis factor (TNF) related proteins (CTRPs), a newly discovered adipokine family with conservative structure and wide distribution, has attracted increasing attention. The CTRP family consists of more than 15 members which fall into the characteristic C1q domain. Increasing studies have demonstrated that CTRPs are involved in the onset and development of inflammation and metabolism as well as related diseases, including myocardial infarction, sepsis and tumors. Here, we first clarified the characteristic domains of CTRPs, and then elucidated their roles in inflammatory-related diseases. Taken together, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.
Humans ; Complement C1q/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Inflammation/metabolism* ; Myocardial Infarction

OBJECTIVETo establish and optimize methods to detect the immune complexes (IC) of hepatitis B virus directly.

METHODSA C1q solid phase ELISA, mouse anti-HBs MAb solid phase ELISA and the complement consumption assay were established to detect the IC and these methods were optimized.

RESULTSAll the three methods were highly sensitive, specific and reproducible. The C1q used for coating tended to lose its activity easily at room temperature. Although strict requirements are needed for the raw and processed materials for complement consumption assay and the process of manipulation is complex, it can quantitatively detect IC. Comparing to the C1q solid ELISA and complement consumption assay, the mouse anti-HBs MAb solid phase ELISA has its own merits: convenience and stability.

CONCLUSIONMouse anti-HBs MAb solid phase ELISA is the best way to detect IC directly.

Complement C1q ; analysis ; Complement Fixation Tests ; methods ; Enzyme-Linked Immunosorbent Assay ; methods ; Hepatitis B ; blood ; Humans ; Reproducibility of Results

Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on complement activation by aPL, we surveyed C1q and factor H binding, and complement activation by aPL, either coated on microtitre plates or in liposomes. Both C1q and factor H bound to all aPL tested, and competed directly with each other for binding. All the aPL activated the complement classical pathway, but negligibly the alternative pathway, consistent with accepted roles of C1q and factor H. However, in this system, factor H, by competing directly with C1q for binding to aPL, acts as a direct regulator of the complement classical pathway. This regulatory mechanism is distinct from its action on the alternative pathway. Regulation of classical pathway activation by factor H was confirmed by measuring C4 activation by aPL in human sera in which the C1q:factor H molar ratio was adjusted over a wide range. Thus factor H, which is regarded as a down-regulator only of the alternative pathway, has a distinct role in downregulating activation of the classical complement pathway by aPL. A factor H homologue, β2-glycoprotein-1, also strongly inhibits C1q binding to cardiolipin. Recombinant globular domains of C1q A, B and C chains bound aPL similarly to native C1q, confirming that C1q binds aPL via its globular heads.
Animals ; Complement Activation ; Complement C1q ; chemistry ; metabolism ; Complement Factor H ; metabolism ; Humans ; Immunoglobulin G ; metabolism ; Mice ; Phospholipids ; chemistry ; metabolism ; Protein Binding

Objective: To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods: The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney U test and Fisher's exact probability test were used for comparison between the groups. Results: Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) vs. 7 (3, 12) years, Z=-2.52, P=0.011), a lower preceding infection rate (45% (9/20) vs. 11/13, P=0.032) and lower spontaneous remission rate (0 vs. 4/13, P=0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 vs. 5/15, P=0.031) and low albumin levels at renal biopsy ((25±6) vs. (29±7) g/L, t=2.14, P=0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all P>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) vs. 6.0 (2.5, 22.3) months, Z=-2.27, P=0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all P>0.05). Conclusion: Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.
Autoantibodies ; Child ; Complement C1q/metabolism* ; Female ; Glomerulonephritis, Membranous/drug therapy* ; Humans ; Immunoglobulin A/immunology* ; Immunoglobulin G ; Kidney Glomerulus ; Male ; Retrospective Studies

BACKGROUND: C1q nephropathy (C1qN) is a controversial diagnostic entity defined by Jennette and Hipp in 1985. The prevalence is very low and a few large scale studies have been reported. Application of the criteria for clinical diagnostics of C1qN may cause confusion with other glomerulonephropathies, such as minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). In order to clarify the confusion with glomerulonephropathies, we did this study to identify the clinicopathological characteristics and the exact disease entity of C1qN. METHODS: A total of 5,258 kidney biopsies at Kangnam St Mary's Hospital were reviewed. Twenty three cases (0.44%) met the criteria of C1qN. Twenty eight cases showing dominant C1q deposits without electron dense depostis (EDD) grouped as C1q+EDD-, and previously diagnosed typical cases of MCD and FSGS were selected for this study. Four groups were compared to each other with regard to the clinical and pathological aspects of the disease. RESULTS: C1qN patients had an average age of 30.4 years. Eighteen were males and 5 were females. Eighty seven percent had proteinuria and 18% had hematuria. By electron microscopy analysis, 100% had mesangial EDD and 47.8% showed foot process effacement. C1qN had some significant differences compared with C1q+EDD-, MCD and FSGS. CONCLUSIONS: C1qN is clinically and morphologically different from MCD and FSGS. However, additional long term studies are needed to fully define C1qN from other glomerulonephritis with C1q deposits.
Biopsy ; Complement C1q ; Corneal Dystrophies, Hereditary ; Electrons ; Female ; Foot ; Glomerulonephritis ; Glomerulosclerosis, Focal Segmental ; Hematuria ; Humans ; Kidney ; Male ; Microscopy, Electron ; Nephrosis, Lipoid ; Phenanthridines ; Prevalence ; Proteinuria

C1q nephropathy is a rare glomerular disease, defined by characteristic mesangial C1q immune deposition seen in immunofluorescence microscopy with no serological evidence of systemic lupus erythematosus. C1q nephropathy can be diagnosed with a subsequent biopsy, as with IgA nephropathy. There are some cases with an initial diagnosis of hematuria and proteinuria with minimal disease changes, focal segmental glomerulonephritis, and mesangial proliferative glomerulonephritis, but lacking C1q nephropathy, in which C1q deposition on immunofluorescence subsequently develops. We report a case that was diagnosed as diffuse mesangial proliferative glomerulonephritis, but a subsequent biopsy showed C1q nephropathy, with C1q deposition in both immunohistochemistry and electron microscopy (EM). We treated the C1q nephropathy with methylprednisolone and confirmed the disappearance of C1q depositions by both immunohistochemistry and EM in a follow-up biopsy.
Biopsy ; Complement C1q ; Diagnosis ; Fluorescent Antibody Technique ; Follow-Up Studies ; Glomerulonephritis ; Glomerulonephritis, IGA ; Hematuria ; Immunohistochemistry ; Lupus Erythematosus, Systemic ; Methylprednisolone ; Microscopy, Electron ; Microscopy, Fluorescence ; Proteinuria

BACKGROUNDLupus hepatitis is yet to be characterized based on its clinical features and is often difficult to differentially diagnose from other liver diseases. We aimed to elucidate clinical, histopathological and immunopathological features of lupus hepatitis and to evaluate primarily the effectiveness of liver immunopathological manifestations on differential diagnosis of lupus hepatitis from other liver diseases.

METHODSA retrospective study was performed to analyze clinical features of lupus hepatitis in 47 patients out of 504 inpatients with systemic lupus erythematosus (SLE) in First Affiliated Hospital of Sun Yat-sen University, China from May 2006 to July 2009, and to evaluate the association between lupus hepatitis and SLE activity. Additionally, liver histopathological changes by hematoxylin and eosin (HE) staining and immunopathological changes by direct immunofluorescence test in 10 lupus hepatitis cases were analyzed and compared to those in 16 patients with other liver diseases in a prospective study.

RESULTSOf 504 SLE patients, 47 patients (9.3%) were diagnosed to have lupus hepatitis. The prevalence of lupus hepatitis in patients with active SLE was higher than that in those with inactive SLE (11.8% vs. 3.2%, P < 0.05). The incidence of hematological abnormalities in patients with lupus hepatitis was higher than that in those without lupus hepatitis (40.4% vs. 21.7%, P < 0.05), such as leucocytes count (2.92×10(9)/L vs. 5.48×10(9)/L), platelets count (151×10(9)/L vs. 190×10(9)/L), serum C3 and C4 (0.34 g/L vs. 0.53 g/L; 0.06 g/L vs. 0.09 g/L) (P < 0.05); 45 of 47 (95.7%) lupus hepatitis patients showed 1 upper limit of normal (ULN) < serum ALT level < 5 ULN. The liver histopathological features in patients with lupus hepatitis were miscellaneous and non-specific, similar to those in other liver diseases, but liver immunopathological features showed positive intense deposits of complement 1q in 7/10 patients with lupus hepatitis and negative complement 1q deposits in all patients with other liver diseases (Fisher's exact test, P = 0.011).

CONCLUSIONSLupus hepatitis was not infrequent in active SLE patients which would be one of the indices indicating SLE activity. Positive intense deposit of complement 1q in liver may be a characteristic immunopathological feature of lupus hepatitis, which provides a new way to differentially diagnose lupus hepatitis from other liver diseases.

Adolescent ; Adult ; Aged ; Child ; Cohort Studies ; Complement C1q ; analysis ; Female ; Hepatitis, Autoimmune ; etiology ; immunology ; pathology ; Humans ; Liver ; pathology ; Lupus Erythematosus, Systemic ; complications ; Male ; Middle Aged ; Retrospective Studies