Human immunodeficiency virus (HIV) infection weakens immunity. Monitoring the immune status of the patient has become an important aspect of evaluating the progression of the disease and informing follow-up after treatment. Estimation of CD4 counts is quite costly and requires expertise in flow cytometry. In certain pathologies, free light chains (FLCs) are secreted in serum and urine and the magnitude can be used to monitor the severity, progression, and therapeutic monitoring of the disease. Urine as a specimen proves cost-effective and presents reduced risks during sample collection. The stability of light chains in urine at room temperature over extended periods simplifies the management of sample transportation as well. Hence, a pilot cross-sectional study was planned to evaluate the levels of urinary immunoglobulins in patients with HIV. The study was conducted at PGIMER, Dr. Ram Manohar Lohia Hospital (presently ABVIMS), New Delhi. Sixty-nine consecutive ART-naive HIV patients aged between 18 and 40 years and 69 age- and sex-matched healthy controls were included in the study. Urinary FLC kappa (κ) and lambda (λ) were measured using an immunoglobulin ELISA kit. Baseline urinary κ light chain levels were significantly higher in cases when compared with controls (p < .001) and were found to be increased with increasing WHO immunological classes (p < .001) and inversely related to CD4 cell count. However, no significant difference in mean urinary λ immunoglobulin light chain between cases and controls was found and no correlation with CD4 cell count or with stages of WHO immunological classification of HIV disease was observed. It is suggested that urinary free κ chain measurements combined with serum light chain measurements may be a useful marker in the follow-up and monitoring of response to therapies in patients with HIV where testing by flow cytometry is not available.

Kappa free light chains (κ-FLC) in the cerebrospinal fluid (CSF) are an emerging biomarker in multiple sclerosis (MS).
To investigate whether κ-FLC index has similar diagnostic value in patients with primary progressive multiple sclerosis (PPMS) compared to oligoclonal bands (OCB).
Patients with PPMS were recruited through 11 MS centres across 7 countries. κ-FLC were measured by immunonephelometry/-turbidimetry. OCB were determined by isoelectric focusing and immunofixation.
A total of 174 patients (mean age of 52±11 years, 51% males) were included. κ-FLC index using a cut-off of 6.1 was positive in 161 (93%) and OCB in 153 (88%) patients.
κ-FLC index shows similar diagnostic sensitivity than OCB in PPMS.

OBJECTIVE: To explore the clinical and pathological features of light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-LC).
METHODS: From January 2010 to December 2022, patients who were diagnosed with PGNMID-LC were selected, and their clinical and pathological features were retrospectively analysed.
RESULTS: Three males aged 42-61 years old were enrolled. Hypertension was present in three patients, oedema in three patients, anaemia in two patients, proteinuria in three patients, nephrotic syndrome in one patient, microscopic haematuria in three patients, renal insufficiency in two patients and hypocomplementaemia of C3 in one patient. Elevated serum-free LC ratios and plasmacytosis on bone marrow smears were observed in three patients, and κ was identified by serum protein immunofixation electrophoresis in one patient. Renal biopsy showed membranoproliferative glomerulonephritis in two patients and endocapillary proliferative glomerulonephritis in one patient on light microscopy. Immunofluorescence indicated restricted κ LC and C3 distributed in glomeruli. By electron microscopy, electron-dense deposits without substructure were identified predominantly in the mesangial and subendothelial regions and were variable in the subepithelial region. Two patients were treated with plasma cell-directed chemotherapy and achieved haematological complete response or very good partial response, and one of them achieved a renal status of complete remission. One patient treated with immunosuppressive therapy only did not achieve haematological or renal remission.
CONCLUSIONS: PGNMID-LC is a rare and uniform disease with a high frequency of a detectable pathogenic plasma cell clone and is characterised by glomerular deposition of restricted LC and C3 in renal pathology. Plasma cell-directed chemotherapy may improve haematological and renal prognosis.

BACKGROUND: Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity.
METHODS: Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated.
RESULTS: A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3).
CONCLUSIONS: κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors.
BACKGROUND: This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.

BACKGROUND: CSF free light chains help diagnose multiple sclerosis, but no data is available on the Asian population. Our objective was to study the diagnostic utility of CSF free light chains for diagnosing multiple sclerosis in Indian patients.
METHODS: Prospective multicentric case-control study. Cases included those who were tested for oligoclonal bands and fulfilled the modified McDonald criteria 2017 for multiple sclerosis and clinically isolated syndromes. Those tested for oligoclonal bands (OCB) but with other diagnoses- inflammatory and non-inflammatory were included as controls. Clinical details were collected from electronic medical records. CSF and serum kappa and lambda free light chains were measured, apart from oligoclonal bands, immunoglobulin, and albumin in paired serum and CSF samples.
RESULTS: There were 70 patients (31 cases and 39 controls). The mean age was 43.41(SD 16.073) years, and 43(61.4%) were females. CSF kappa showed highest specificity 97.4%, at a cut off 2.06 mg/L (sensitivity 71%) and highest sensitivity 90.3%, at a cut off 0.47 mg/L (specificity 79.5%). Best balance of sensitivity and specificity for CSF kappa was seen at a cut-off of ≥ 0.63 mg/L {sensitivity 87·1 (CI - 70.17-96.37), and specificity 87·18 (CI -72.57-95.70)}. The ratio of Kappa/lambda showed highest specificity of 100%(similar to OCB) with a sensitivity of 71% at a cut off of 1.72. The ratio of sum of kappa and lambda light chains, and Qalb (∑CSF FLC/Qalb), showed the highest specificity (94.87%)among the blood brain barrier corrected ratios.
CONCLUSIONS: This study showed that the diagnostic utility of CSF kappa was comparable to OCB to diagnose multiple sclerosis in sensitivity, but not specificity, so can be a screening test before testing for OCB in our population.

暂无摘要。

Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands\' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.
We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).
One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p = 0.123 and p = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p = 0.065). In the multivariate analysis model, female gender (p = 0.003), young age (p = 0.013), and evidence of disease activity (p < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.
KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.
This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.

Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus.
To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases.
A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite.
A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups (p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index.
Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

Some misfolded proteins, e.g., immunoglobulin monoclonal free light chains (FLC), tend to form fibrils. Protein deposits in tissue may lead to amyloidosis and dysfunction of different organs. There is currently no technique allowing for the identification of FLC that are prone to aggregate. The development of such a method would enable the early selection of patients at high risk of developing amyloidosis. The aim of this study was to investigate whether silver nanoparticles (AgNPs) could be a useful tool to study the process of aggregation of FLC and their susceptibility to form the protein deposits. Mixtures of AgNPs and urine samples from patients with multiple myeloma were prepared. To evaluate the aggregation process of nanoparticles coated with proteins, UV-visible spectroscopy, transmission electron microscopy, and the original laser light scattering method were used. It has been shown that some clones of FLC spontaneously triggered aggregation of the nanoparticles, while in the presence of others, the nanoparticle solution became hyperstable. This is probably due to the structure of the chains themselves, unique protein-AgNPs interactions and perhaps correlates with the tendency of some FLC clones to form deposits. Nanoparticle technology has proven to be helpful in identifying clones of immunoglobulin FLC that tend to aggregate.

Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn.
This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed.
Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %.
The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients\' renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.